ABSTRACT
The increasing availability of time series data depicting the evolution of physical system properties has prompted the development of methods focused on extracting insights into the system behavior over time, discerning whether it stems from deterministic or stochastic dynamical systems. Surrogate data testing plays a crucial role in this process by facilitating robust statistical assessments. This ensures that the observed results are not mere occurrences by chance, but genuinely reflect the inherent characteristics of the underlying system. The initial process involves formulating a null hypothesis, which is tested using surrogate data in cases where assumptions about the underlying distributions are absent. A discriminating statistic is then computed for both the original data and each surrogate data set. Significantly deviating values between the original data and the surrogate data ensemble lead to the rejection of the null hypothesis. In this work, we present various surrogate methods designed to assess specific statistical properties in random processes. Specifically, we introduce methods for evaluating the presence of autodependencies and nonlinear dynamics within individual processes, using Information Storage as a discriminating statistic. Additionally, methods are introduced for detecting coupling and nonlinearities in bivariate processes, employing the Mutual Information Rate for this purpose. The surrogate methods introduced are first tested through simulations involving univariate and bivariate processes exhibiting both linear and nonlinear dynamics. Then, they are applied to physiological time series of Heart Period (RR intervals) and respiratory flow (RESP) variability measured during spontaneous and paced breathing. Simulations demonstrated that the proposed methods effectively identify essential dynamical features of stochastic systems. The real data application showed that paced breathing, at low breathing rate, increases the predictability of the individual dynamics of RR and RESP and dampens nonlinearity in their coupled dynamics.
ABSTRACT
Wearable health devices (WHDs) are rapidly gaining ground in the biomedical field due to their ability to monitor the individual physiological state in everyday life scenarios, while providing a comfortable wear experience. This study introduces a novel wearable biomedical device capable of synchronously acquiring electrocardiographic (ECG), photoplethysmographic (PPG), galvanic skin response (GSR) and motion signals. The device has been specifically designed to be worn on a finger, enabling the acquisition of all biosignals directly on the fingertips, offering the significant advantage of being very comfortable and easy to be employed by the users. The simultaneous acquisition of different biosignals allows the extraction of important physiological indices, such as heart rate (HR) and its variability (HRV), pulse arrival time (PAT), GSR level, blood oxygenation level (SpO2), and respiratory rate, as well as motion detection, enabling the assessment of physiological states, together with the detection of potential physical and mental stress conditions. Preliminary measurements have been conducted on healthy subjects using a measurement protocol consisting of resting states (i.e., SUPINE and SIT) alternated with physiological stress conditions (i.e., STAND and WALK). Statistical analyses have been carried out among the distributions of the physiological indices extracted in time, frequency, and information domains, evaluated under different physiological conditions. The results of our analyses demonstrate the capability of the device to detect changes between rest and stress conditions, thereby encouraging its use for assessing individuals' physiological state. Furthermore, the possibility of performing synchronous acquisitions of PPG and ECG signals has allowed us to compare HRV and pulse rate variability (PRV) indices, so as to corroborate the reliability of PRV analysis under stationary physical conditions. Finally, the study confirms the already known limitations of wearable devices during physical activities, suggesting the use of algorithms for motion artifact correction.
Subject(s)
Electrocardiography , Fingers , Galvanic Skin Response , Heart Rate , Photoplethysmography , Wearable Electronic Devices , Humans , Monitoring, Physiologic/instrumentation , Signal Processing, Computer-Assisted , Male , Adult , FemaleABSTRACT
The concept of self-predictability plays a key role for the analysis of the self-driven dynamics of physiological processes displaying richness of oscillatory rhythms. While time domain measures of self-predictability, as well as time-varying and local extensions, have already been proposed and largely applied in different contexts, they still lack a clear spectral description, which would be significantly useful for the interpretation of the frequency-specific content of the investigated processes. Herein, we propose a novel approach to characterize the linear self-predictability (LSP) of Gaussian processes in the frequency domain. The LSP spectral functions are related to the peaks of the power spectral density (PSD) of the investigated process, which is represented as the sum of different oscillatory components with specific frequency through the method of spectral decomposition. Remarkably, each of the LSP profiles is linked to a specific oscillation of the process, and it returns frequency-specific measures when integrated along spectral bands of physiological interest, as well as a time domain self-predictability measure with a clear meaning in the field of information theory, corresponding to the well-known information storage, when integrated along the whole frequency axis. The proposed measure is first illustrated in a theoretical simulation, showing that it clearly reflects the degree and frequency-specific location of predictability patterns of the analyzed process in both time and frequency domains. Then, it is applied to beat-to-beat time series of arterial compliance obtained in young healthy subjects. The results evidence that the spectral decomposition strategy applied to both the PSD and the spectral LSP of compliance identifies physiological responses to postural stress of low and high frequency oscillations of the process which cannot be traced in the time domain only, highlighting the importance of computing frequency-specific measures of self-predictability in any oscillatory physiologic process.
ABSTRACT
OBJECTIVE: Concepts of Granger causality (GC) and Granger autonomy (GA) are central to assess the dynamics of coupled physiologic processes. While causality measures have been already proposed and largely applied in time and frequency domains, measures quantifying self-dependencies are still limited to the time-domain formulation and lack of a clear spectral representation. METHODS: We embed into the classical linear parametric framework for computing GC from a driver random process X to a target process Y a measure of Granger Isolation (GI) quantifying the part of the dynamics of Y not originating from X, and a new spectral measure of GA assessing frequency-specific patterns of self-dependencies in Y. The framework is formulated in a way such that the full-frequency integration of the spectral GC, GI and GA measures returns the corresponding time-domain measures. The measures are illustrated in theoretical simulations and applied to time series of mean arterial pressure and cerebral blood flow velocity obtained in subjects prone to develop postural syncope and healthy controls. RESULTS: simulations show that GI is complementary to GC but not trivially related to it, while GA reflects the regularity of the internal dynamics of the analyzed target process. In the application to cerebrovascular interactions, spectral GA quantified the physiological response to postural stress of slow cerebral blood flow oscillations, while spectral GC and GI detected an altered response to postural stress in subjects prone to syncope, likely related to impaired cerebral autoregulation. CONCLUSION AND SIGNIFICANCE: The new spectral measures of GI and GA are useful complements to GC for the analysis of interacting oscillatory processes, and detect physiological and pathological responses to postural stress which cannot be traced in the time domain. The thorough assessment of causality, isolation and autonomy opens new perspectives for the analysis of coupled biological processes in both physiological and clinical investigations.
ABSTRACT
We present an approach to assess redundant and synergistic interactions in network systems via the information-theoretic analysis of multivariate physiological processes. The approach sets up a strategy to decompose the information shared between the present states of a group of random processes and their own past states into unique contributions arising from the past of subgroups of processes and redundant and synergistic contributions arising from the dynamic interaction among the subgroups. The method is illustrated in a theoretical example of linearly interacting Gaussian processes, showing that redundancy and synergy are related mostly to unidirectional coupling and to bidirectional coupling with internal dynamics. It is then applied to the network of short-term heart period, arterial pressure and respiratory variability probed in healthy subjects, showing that redundancy and synergy prevail respectively in cardiorespiratory interactions and in cardiovascular interactions in the resting state, and that postural stress increases the predictive information and the redundancy of physiological interactions.
Subject(s)
Cardiovascular System , Heart , Humans , Blood Pressure/physiology , Heart Rate/physiology , Heart/physiology , Arterial PressureABSTRACT
The trend toward personalized medicine necessitates drawing conclusions from descriptive indexes of physiopathological states estimated from individual recordings of biomedical signals, using statistical analyses that focus on subject-specific differences between experimental conditions. In this context, the present work introduces an approach to assess functional connectivity in brain and physiologic networks by pairwise information-theoretic measures of coupling between signals, whose significance and variations between conditions are statistically validated on a single-subject basis through the use of surrogate and bootstrap data analyses. The approach is illustrated on single-subject recordings of (i) resting-state functional magnetic resonance imaging (rest-fMRI) signals acquired in a pediatric patient with hepatic encephalography associated to a portosystemic shunt and undergoing liver vascular shunt correction, and of (ii) cardiovascular and cerebrovascular time series acquired at rest and during head-up tilt in a subject suffering from orthostatic intolerance.
Subject(s)
Brain Mapping , Brain , Humans , Child , Brain Mapping/methods , Brain/diagnostic imaging , Brain/physiology , Magnetic Resonance Imaging/methods , Research Design , Time FactorsABSTRACT
Heart rate variability results from the coupled activity of the cardiovascular and cardiorespiratory systems, which have their own internal regulation mechanisms but also interact with each other and with the autonomic nervous system to maintain homeostasis. In this work, the assessment of these physiological mechanisms is carried out decomposing the Mutual Information Rate (MIR), an information-theoretic measure of the interdependence between coupled processes, into terms of entropy rate or conditional mutual information related respectively to complexity and causality measures. These measures are computed using a non-parametric approach based on nearest-neighbors. The proposed framework is first tested on simulated autoregressive processes and then applied to experimental data consisting of heart period and respiratory time series measured in healthy subjects monitored at rest and during head-up tilt. Our results evidence that MIR decomposition is able to highlight the interdependence of short-term physiological mechanisms of cardiorespiratory interactions during postural stress.
Subject(s)
Cardiovascular System , Heart , Humans , Blood Pressure/physiology , Heart/physiology , Respiration , Respiratory RateABSTRACT
In this work, we perform a comparative analysis of discrete- and continuous-time estimators of information-theoretic measures quantifying the concept of memory utilization in short-term heart rate variability (HRV). Specifically, considering heartbeat intervals in discrete time we compute the measure of information storage (IS) and decompose it into immediate memory utilization (IMU) and longer memory utilization (MU) terms; considering the timings of heartbeats in continuous time we compute the measure of MU rate (MUR). All measures are computed through model-free approaches based on nearest neighbor entropy estimators applied to the HRV series of a group of 15 healthy subjects measured at rest and during postural stress. We find, moving from rest to stress, statistically significant increases of the IS and the IMU, as well as of the MUR. Our results suggest that both discrete-time and continuous-time approaches can detect the higher predictive capacity of HRV occurring with postural stress, and that such increased memory utilization is due to fast mechanisms likely related to sympathetic activation.
Subject(s)
Memory, Short-Term , Humans , Heart Rate/physiology , Entropy , Healthy VolunteersABSTRACT
Network Physiology is a rapidly growing field of study that aims to understand how physiological systems interact to maintain health. Within the information theory framework the information storage (IS) allows to measure the regularity and predictability of a dynamic process under stationarity assumption. However, this assumption does not allow to track over time the transient pathways occurring in the dynamical activity of a physiological system. To address this limitation, we propose a time-varying approach based on the recursive least squares algorithm (RLS) for estimating IS at each time instant, in non-stationary conditions. We tested this approach in simulated time-varying dynamics and in the analysis of electroencephalographic (EEG) signals recorded from healthy volunteers and timed with the heartbeat to investigate brain-heart interactions. In simulations, we show that the proposed approach allows to track both abrupt and slow changes in the information stored in a physiological system. These changes are reflected in its evolution and variability over time. The analysis of brain-heart interactions reveals marked differences across the cardiac cycle phases of the variability of the time-varying IS. On the other hand, the average IS values exhibit a weak modulation over parieto-occiptal areas of the scalp. Our study highlights the importance of developing more advanced methods for measuring IS that account for non-stationarity in physiological systems. The proposed time-varying approach based on RLS represents a useful tool for identifying spatio-temporal dynamics within the neurocardiac system and can contribute to the understanding of brain-heart interactions.
ABSTRACT
Keeping up with the shift towards personalized neuroscience essentially requires the derivation of meaningful insights from individual brain signal recordings by analyzing the descriptive indexes of physio-pathological states through statistical methods that prioritize subject-specific differences under varying experimental conditions. Within this framework, the current study presents a methodology for assessing the value of the single-subject fingerprints of brain functional connectivity, assessed both by standard pairwise and novel high-order measures. Functional connectivity networks, which investigate the inter-relationships between pairs of brain regions, have long been a valuable tool for modeling the brain as a complex system. However, their usefulness is limited by their inability to detect high-order dependencies beyond pairwise correlations. In this study, by leveraging multivariate information theory, we confirm recent evidence suggesting that the brain contains a plethora of high-order, synergistic subsystems that would go unnoticed using a pairwise graph structure. The significance and variations across different conditions of functional pairwise and high-order interactions (HOIs) between groups of brain signals are statistically verified on an individual level through the utilization of surrogate and bootstrap data analyses. The approach is illustrated on the single-subject recordings of resting-state functional magnetic resonance imaging (rest-fMRI) signals acquired using a pediatric patient with hepatic encephalopathy associated with a portosystemic shunt and undergoing liver vascular shunt correction. Our results show that (i) the proposed single-subject analysis may have remarkable clinical relevance for subject-specific investigations and treatment planning, and (ii) the possibility of investigating brain connectivity and its post-treatment functional developments at a high-order level may be essential to fully capture the complexity and modalities of the recovery.
ABSTRACT
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.
Subject(s)
Cardiovascular System , Humans , Syncope , Heart , Blood Pressure/physiology , Arterial Pressure , Heart Rate/physiology , Baroreflex/physiology , Cerebrovascular Circulation/physiologyABSTRACT
The properties of cardio-respiratory coupling (CRC) are affected by various pathological conditions related to the cardiovascular and/or respiratory systems. In heart failure, one of the most common cardiac pathological conditions, the degree of CRC changes primarily depend on the type of heart-rhythm alterations. In this work, we investigated CRC in heart-failure patients, applying measures from information theory, i.e., Granger Causality (GC), Transfer Entropy (TE) and Cross Entropy (CE), to quantify the directed coupling and causality between cardiac (RR interval) and respiratory (Resp) time series. Patients were divided into three groups depending on their heart rhythm (sinus rhythm and presence of low/high number of ventricular extrasystoles) and were studied also after cardiac resynchronization therapy (CRT), distinguishing responders and non-responders to the therapy. The information-theoretic analysis of bidirectional cardio-respiratory interactions in HF patients revealed the strong effect of nonlinear components in the RR (high number of ventricular extrasystoles) and in the Resp time series (respiratory sinus arrhythmia) as well as in their causal interactions. We showed that GC as a linear model measure is not sensitive to both nonlinear components and only model free measures as TE and CE may quantify them. CRT responders mainly exhibit unchanged asymmetry in the TE values, with statistically significant dominance of the information flow from Resp to RR over the opposite flow from RR to Resp, before and after CRT. In non-responders this asymmetry was statistically significant only after CRT. Our results indicate that the success of CRT is related to corresponding information transfer between the cardiac and respiratory signal quantified at baseline measurements, which could contribute to a better selection of patients for this type of therapy.
ABSTRACT
Odorant processing presents multiple parallels across animal species, and insects became relevant models for the study of olfactory coding because of the tractability of the underlying neural circuits. Within the insect brain, odorants are received by olfactory sensory neurons and processed by the antennal lobe network. Such a network comprises multiple nodes, named glomeruli, that receive sensory information and are interconnected by local interneurons participating in shaping the neural representation of an odorant. The study of functional connectivity between the nodes of a sensory network in vivo is a challenging task that requires simultaneous recording from multiple nodes at high temporal resolutions. Here, we followed the calcium dynamics of antennal lobe glomeruli and applied Granger causality analysis to assess the functional connectivity among network nodes in the presence and absence of an odorous stimulus. This approach revealed the existence of causal connectivity links between antennal lobe glomeruli in the absence of olfactory stimulation, while at odor arrival, the connectivity network's density increased and became stimulus-specific. Thus, such an analytical approach may provide a new tool for the investigation of neural network plasticity in vivo.
ABSTRACT
The increasing interest in innovative solutions for health and physiological monitoring has recently fostered the development of smaller biomedical devices. These devices are capable of recording an increasingly large number of biosignals simultaneously, while maximizing the user's comfort. In this study, we have designed and realized a novel wearable multisensor ring-shaped probe that enables synchronous, real-time acquisition of photoplethysmographic (PPG) and galvanic skin response (GSR) signals. The device integrates both the PPG and GSR sensors onto a single probe that can be easily placed on the finger, thereby minimizing the device footprint and overall size. The system enables the extraction of various physiological indices, including heart rate (HR) and its variability, oxygen saturation (SpO2), and GSR levels, as well as their dynamic changes over time, to facilitate the detection of different physiological states, e.g., rest and stress. After a preliminary SpO2 calibration procedure, measurements have been carried out in laboratory on healthy subjects to demonstrate the feasibility of using our system to detect rapid changes in HR, skin conductance, and SpO2 across various physiological conditions (i.e., rest, sudden stress-like situation and breath holding). The early findings encourage the use of the device in daily-life conditions for real-time monitoring of different physiological states.
Subject(s)
Photoplethysmography , Wearable Electronic Devices , Humans , Photoplethysmography/methods , Monitoring, Physiologic , Heart Rate/physiology , Galvanic Skin ResponseABSTRACT
Nonlinear markers of coupling strength are often utilized to typify cardiorespiratory and cerebrovascular regulations. The computation of these indices requires techniques describing nonlinear interactions between respiration (R) and heart period (HP) and between mean arterial pressure (MAP) and mean cerebral blood velocity (MCBv). We compared two model-free methods for the assessment of dynamic HP-R and MCBv-MAP interactions, namely the cross-sample entropy (CSampEn) and k-nearest-neighbor cross-unpredictability (KNNCUP). Comparison was carried out first over simulations generated by linear and nonlinear unidirectional causal, bidirectional linear causal, and lag-zero linear noncausal models, and then over experimental data acquired from 19 subjects at supine rest during spontaneous breathing and controlled respiration at 10, 15, and 20 breaths·minute-1 as well as from 13 subjects at supine rest and during 60° head-up tilt. Linear markers were computed for comparison. We found that: (i) over simulations, CSampEn and KNNCUP exhibit different abilities in evaluating coupling strength; (ii) KNNCUP is more reliable than CSampEn when interactions occur according to a causal structure, while performances are similar in noncausal models; (iii) in healthy subjects, KNNCUP is more powerful in characterizing cardiorespiratory and cerebrovascular variability interactions than CSampEn and linear markers. We recommend KNNCUP for quantifying cardiorespiratory and cerebrovascular coupling.
ABSTRACT
This work presents a comparison between different approaches for the model-free estimation of information-theoretic measures of the dynamic coupling between short realizations of random processes. The measures considered are the mutual information rate (MIR) between two random processes X and Y and the terms of its decomposition evidencing either the individual entropy rates of X and Y and their joint entropy rate, or the transfer entropies from X to Y and from Y to X and the instantaneous information shared by X and Y. All measures are estimated through discretization of the random variables forming the processes, performed either via uniform quantization (binning approach) or rank ordering (permutation approach). The binning and permutation approaches are compared on simulations of two coupled non-identical Hènon systems and on three datasets, including short realizations of cardiorespiratory (CR, heart period and respiration flow), cardiovascular (CV, heart period and systolic arterial pressure), and cerebrovascular (CB, mean arterial pressure and cerebral blood flow velocity) measured in different physiological conditions, i.e., spontaneous vs paced breathing or supine vs upright positions. Our results show that, with careful selection of the estimation parameters (i.e., the embedding dimension and the number of quantization levels for the binning approach), meaningful patterns of the MIR and of its components can be achieved in the analyzed systems. On physiological time series, we found that paced breathing at slow breathing rates induces less complex and more coupled CR dynamics, while postural stress leads to unbalancing of CV interactions with prevalent baroreflex coupling and to less complex pressure dynamics with preserved CB interactions. These results are better highlighted by the permutation approach, thanks to its more parsimonious representation of the discretized dynamic patterns, which allows one to explore interactions with longer memory while limiting the curse of dimensionality.
Subject(s)
Cardiovascular System , Heart Rate/physiology , Blood Pressure/physiology , Heart/physiology , RespirationABSTRACT
Understanding how different areas of the human brain communicate with each other is a crucial issue in neuroscience. The concepts of structural, functional and effective connectivity have been widely exploited to describe the human connectome, consisting of brain networks, their structural connections and functional interactions. Despite high-spatial-resolution imaging techniques such as functional magnetic resonance imaging (fMRI) being widely used to map this complex network of multiple interactions, electroencephalographic (EEG) recordings claim high temporal resolution and are thus perfectly suitable to describe either spatially distributed and temporally dynamic patterns of neural activation and connectivity. In this work, we provide a technical account and a categorization of the most-used data-driven approaches to assess brain-functional connectivity, intended as the study of the statistical dependencies between the recorded EEG signals. Different pairwise and multivariate, as well as directed and non-directed connectivity metrics are discussed with a pros-cons approach, in the time, frequency, and information-theoretic domains. The establishment of conceptual and mathematical relationships between metrics from these three frameworks, and the discussion of novel methodological approaches, will allow the reader to go deep into the problem of inferring functional connectivity in complex networks. Furthermore, emerging trends for the description of extended forms of connectivity (e.g., high-order interactions) are also discussed, along with graph-theory tools exploring the topological properties of the network of connections provided by the proposed metrics. Applications to EEG data are reviewed. In addition, the importance of source localization, and the impacts of signal acquisition and pre-processing techniques (e.g., filtering, source localization, and artifact rejection) on the connectivity estimates are recognized and discussed. By going through this review, the reader could delve deeply into the entire process of EEG pre-processing and analysis for the study of brain functional connectivity and learning, thereby exploiting novel methodologies and approaches to the problem of inferring connectivity within complex networks.
ABSTRACT
The study of high order dependencies in complex systems has recently led to the introduction of statistical synergy, a novel quantity corresponding to a form of emergence in which patterns at large scales are not traceable from lower scales. As a consequence, several works in the last years dealt with the synergy and its counterpart, the redundancy. In particular, the O-information is a signed metric that measures the balance between redundant and synergistic statistical dependencies. In spite of its growing use, this metric does not provide insight about the role played by low-order scales in the formation of high order effects. To fill this gap, the framework for the computation of the O-information has been recently expanded introducing the so-called gradients of this metric, which measure the irreducible contribution of a variable (or a group of variables) to the high order informational circuits of a system. Here, we review the theory behind the O-information and its gradients and present the potential of these concepts in the field of network physiology, showing two new applications relevant to brain functional connectivity probed via functional resonance imaging and physiological interactions among the variability of heart rate, arterial pressure, respiration and cerebral blood flow.
ABSTRACT
Heart Rate Variability (HRV) and Blood Pressure Variability (BPV) are widely employed tools for characterizing the complex behavior of cardiovascular dynamics. Usually, HRV and BPV analyses are carried out through short-term (ST) measurements, which exploit ~five-minute-long recordings. Recent research efforts are focused on reducing the time series length, assessing whether and to what extent Ultra-Short-Term (UST) analysis is capable of extracting information about cardiovascular variability from very short recordings. In this work, we compare ST and UST measures computed on electrocardiographic R-R intervals and systolic arterial pressure time series obtained at rest and during both postural and mental stress. Standard time-domain indices are computed, together with entropy-based measures able to assess the regularity and complexity of cardiovascular dynamics, on time series lasting down to 60 samples, employing either a faster linear parametric estimator or a more reliable but time-consuming model-free method based on nearest neighbor estimates. Our results are evidence that shorter time series down to 120 samples still exhibit an acceptable agreement with the ST reference and can also be exploited to discriminate between stress and rest. Moreover, despite neglecting nonlinearities inherent to short-term cardiovascular dynamics, the faster linear estimator is still capable of detecting differences among the conditions, thus resulting in its suitability to be implemented on wearable devices.