- 1Biosignals and Information Theory Laboratory, Department of Engineering, University of Palermo, Palermo, Italy
- 2CMUP LASI, Departamento de Matemática, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
- 3Faculty of Technical Sciences, University of Novi Sad, Novi Sad, Serbia
Understanding the underlying dynamics of complex real-world systems, such as neurophysiological and climate systems, requires quantifying the functional interactions between the system units under different scenarios. This tutorial paper offers a comprehensive description to time, frequency and information-theoretic domain measures for assessing the interdependence between pairs of time series describing the dynamical activities of physical systems, supporting flexible and robust analyses of statistical dependencies and directional relationships. Classical time and frequency domain correlation-based measures, as well as directional approaches derived from the notion of Granger causality, are introduced and discussed, along with information-theoretic measures of symmetrical and directional coupling. Both linear model-based and non-linear model-free estimation approaches are thoroughly described, the latter including binning, permutation, and nearest-neighbour estimators. Special emphasis is placed on the description of a unified framework that establishes a connection between causal and symmetric, as well as spectral and information-theoretic measures. This framework enables the frequency-specific representation of information-theoretic metrics, allowing for a detailed investigation of oscillatory components in bivariate systems. The practical computation of the interaction measures is favoured by presenting a software toolbox and two exemplary applications to cardiovascular and climate data. By bridging theoretical concepts with practical tools, this work enables researchers to effectively investigate a wide range of dynamical behaviours in various real-world scenarios in Network Physiology and beyond.
1 Introduction
A central challenge in the broad field of Network Science consists in deciphering how complex, system-wide dynamics emerge from the interactions among the units of a distributed network (Bashan et al., 2012; Barabási, 2013; Bassett and Sporns, 2017). A key strategy to tackle this problem involves quantifying bivariate interactions, that is, measuring how pairs of individual components influence each other over time. Numerous data-driven methodologies for network inference have been developed to investigate interactions emerging from time-resolved data, enabling researchers to map the functional interdependencies that drive the dynamic behaviours of the investigated systems. For instance, in neuroscience, functional connectivity between pairs of brain regions has often been assessed via correlation-based measures, capturing co-activation patterns linked to cognition and altered in pathological conditions such as Alzheimer and schizophrenia (Buckner et al., 2005; Bassett and Sporns, 2017). In regulatory physiology, the dynamic activity of cardiovascular, cardiorespiratory and cerebrovascular systems has been widely investigated using dynamic measures of complexity and causality in different experimental conditions and patho-physiological states, evidencing well-known behaviours including frequency-specific responses along the baroreflex and the pressure-to-flow link [see, e.g., Schulz et al. (2013); Bari et al. (2016); Porta and Faes (2015); Pernice et al. (2022b); Sparacino et al. (2024a); Cairo et al. (2025)]. Also in very different fields such as earth system science, causal approaches have revealed the presence and importance of directional links, e.g., between sea-surface temperature and fish populations (Sugihara et al., 2012), as well as between atmospheric patterns and air circulation (Runge et al., 2019).
In the context of data-driven network modelling, bivariate interactions have been inferred from pairs of time series describing the dynamic activities of the two investigated systems, and generally assessed by measures of coupling and causality in the time, frequency and/or information-theoretic domains (Pereda et al., 2005; Porta and Faes, 2015; Schulz et al., 2013; Edinburgh et al., 2021; Cliff et al., 2021). Specifically, non-directional coupling relations between time series refer to associations which do not specify the direction of influence, rather look for symmetrical statistical dependencies between them (Faes et al., 2012a; Faes and Nollo, 2013). A common and simple approach to compute non-directional coupling in the time domain is cross-correlation, which measures the similarity between time series as a function of the time lag, capturing synchronous or time-shifted dependencies (Reinsel, 2003; Pereda et al., 2005). While straightforward and computationally efficient, cross-correlation assumes linearity, can be sensitive to noise or temporal misalignment (Cliff et al., 2021) and does not assume causality between the time series. Nevertheless, the principle of causality is fundamental to identify driver-response (i.e., time-lagged) relations between the series. In the linear signal processing framework, this principle has been explored with reference to the concept of Granger causality (GC), originally developed by Wiener (Wiener, 1956) and then made operative by Granger in the context of linear regression models (Granger, 1969). In particular, GC relates the presence of a cause-effect relation to two aspects: the cause must precede the effect in time and must carry unique information about the present value of the effect. This relationship is not symmetrical and can be bidirectional, thus enabling the detection of both directional and reciprocal influences (Bressler and Seth, 2011; Porta and Faes, 2015). Differently from non-directional measures, causality approaches exploiting this concept have allowed focusing on specific directional pathways of interaction within the investigated network, as widely done, e.g., in neurophysiology (Ding et al., 2006; Porta and Faes, 2015; Seth et al., 2015; Koutlis et al., 2021; Charleston-Villalobos et al., 2023; Pernice et al., 2022a; Difrancesco et al., 2023; Pichot et al., 2024), or in climate (Smirnov and Mokhov, 2009; McGraw and Barnes, 2018; Runge et al., 2019) and ecological (Freeman, 1983; Sugihara et al., 2012) sciences.
A limitation of traditional time domain measures of coupling and causality is their lack of frequency resolution, as they capture overall dependencies between two time series without isolating contributions from specific oscillatory components. This represents an issue in fields such as cardiovascular analysis, where physiological signals including heart rate and blood pressure exhibit distinct rhythmic patterns, especially within the low-frequency (LF,
Statistical dependencies among real-world time series can be evaluated using information-theoretic tools. Entropy-based measures of mutual information, mutual information rate and transfer entropy have been largely exploited to assess the overall information shared between two interdependent systems (Shannon, 1948; Cover, 1999), the dynamic interdependence between two systems per unit of time (Gelfand and Yaglom, 1959; Duncan, 1970; Faes et al., 2022; Barà et al., 2023; Antonacci et al., 2025; Pinto et al., 2025a), and the dynamic information transferred to a selected target system from the other connected system (Schreiber, 2000; Wibral et al., 2014; Faes et al., 2015b; 2016a; Shao et al., 2023), respectively. Remarkably, the mutual information rate represents a dynamic version of the mutual information and, as such, reflects the strength of the symmetrical statistical association between two dynamic systems. It has been decomposed into terms with meaningful physical interpretations corresponding to the well-known conditional entropy and transfer entropy measures (Barà et al., 2023; Pinto et al., 2025a). These metrics are closely related to the notions of complexity of individual systems and causality between pairs of systems, and widely exploited in various applications to real data (Faes et al., 2013c; Runge et al., 2019; Martins et al., 2020; Silini et al., 2023; Barà et al., 2023).
Information-theoretic measures have the main advantage of generality, being defined in terms of probability distributions, and can thus be stated in a fully model-free formulation (Ash, 2012). Examples of model-free estimators include the k-nearest neighbour (Kozachenko and Leonenko, 1987; Kraskov et al., 2004), permutation-based (Bandt and Pompe, 2002; Barà et al., 2023) and binning (Darbellay and Vajda, 1999; Cellucci et al., 2005; Azami et al., 2023) approaches. These methods enable the detection of non-linear and consequently more complex relationships, although they require trade-offs in terms of dimensionality, estimation accuracy, computational complexity and sensitivity to parameter choices. Nevertheless, information measures can also be expressed in terms of predictability improvement under the two key assumptions of linearity and joint Gaussianity; if this is the case, their computation relies on parametric autoregressive models (Lütkepohl, 2005; Barnett et al., 2009), whereby concepts of prediction error and conditional entropy, GC and transfer entropy, or spectral coherence and mutual information rate, have been linked to each other in the time and frequency domains (Geweke, 1982; Barnett et al., 2009; Barrett et al., 2010; Chicharro, 2011; Faes et al., 2015b; Porta and Faes, 2015; Faes et al., 2016b). Remarkably, the information-theoretic and spectral formulations are tightly connected thanks to the fulfillment of the spectral integration property, which is essential to allow quantification of these measures with reference to specific oscillatory components contained within spectral bands of interest.
In the wide context of bivariate time series analysis, this work presents a coherent theoretical framework in which measures of coupling and causality in the time, frequency, and information-theoretic domains are thoroughly reviewed and described, emphasizing properties and relations across domains (Section 1). The practical implementation of the measures is favoured by the exploitation of parametric autoregressive models (Section 2), which establish a connection between information-theoretic and spectral formulations under the assumptions of linearity and joint Gaussianity, and model-free approaches (Section 3), including techniques such as coarse-graining of embedding spaces (k-nearest neighbours estimator) or symbolic representations of the observed dynamics (binning and permutation estimators). The software and the codes relevant to the practical computation and statistical validation of the bivariate interaction measures are presented in Section 4, and collected in the BIM (Bivariate information measures) Matlab toolbox available for free download from https://github.com/laurasparacino. To illustrate the behaviour of the discussed measures and to showcase their implementation allowed by the BIM toolbox, illustrative examples are finally reported regarding benchmark applications to cardiovascular and climate time series (Section 5).
2 Framework for the analysis of interactions in bivariate systems
This section first introduces basic concepts of probability related to static and dynamic systems (Section 1.1) (Papoulis and Pillai, 2002). Then, it illustrates well-known correlation-related measures in the time and frequency domains (Section 1.2), as well as measures that implement the concepts of coupling and causality applied to random variables and processes in the field of information-theory (Section 1.3). A schematic overview of these measures, emphasizing the nature (coupling vs. causality) and computation domain (time, frequency, information-theoretic) of the measures as well as their conceptual and mathematical links, is given in Figure 1.
Figure 1. Overview of coupling and causality measures across time, frequency, and information-theoretic domains, as reviewed and discussed in this work. The implementation through linear autoregressive models and model-free approaches is discussed in Section 2 and Section 3, respectively, while the mathematical connection between formulations in the three domains is presented in Section 2.5.
2.1 Basic notions of probability
2.1.1 Static analysis of random variables
A random variable is a mathematical variable whose value is subject to variations due to chance. Specifically, continuous random variables can take values inside an infinite-dimensional set usually denoted as the domain. The generic scalar random variable
The bivariate interactions between the two variables
2.1.2 Dynamic analysis of random processes
Contrarily to static systems, dynamic systems take values over diverse states at different instants of time, thus being explicitly dependent on the flow of time. The evolution over time of these systems can be only described in probabilistic terms using random processes, which can be thought of as sequences of random variables ordered according to time. Formally, the states visited by a generic dynamic system over time are described as a stochastic process
A useful property of stochastic processes is wide-sense stationarity (WSS), which defines the time-invariance of any joint probability density taken from the process. When the process is stationary, its composing variables are identically distributed, meaning that that the probability density is the same at all times; in practice, this allows to pool together the observations measured across time order to estimate the densities, thus enabling the estimation of probabilities from an individual realization of the process, i.e., a single time series (Faes et al., 2016b). For a stationary stochastic process, also the transition probabilities are time-independent, i.e.,
The bivariate interactions between two generic processes
2.2 Correlation-based measures in the time and frequency domain
In the time domain, the simplest way to identify symmetric statistical dependencies between signals is through correlation. The commonly used static approach disregards temporal dependencies and considers the zero-lag interaction between two random variables
where
To account for time-lagged dependencies, the time series are considered as realizations of two random processes
while the CCF in Equation 2 generally a function also of the time instant
The two observed random processes can be studied in the frequency domain in terms of the power spectral density (PSD) matrix of the stationary bivariate random process
The link between the time and frequency domain representations is provided by the Fourier Transform (FT)
where
The coherence (Coh) between the two processes
Since this function is complex-valued, its squared modulus is commonly used to measure the strength of coupling in the frequency domain. Indeed, the magnitude squared coherence,
exploiting Equation 5, it can be shown that the squared Coh is related to the logarithimc TD measure through the relation
In practice, estimation of the PSD from finite-length time series can be achieved through both parametric (Section 2.4) and non-parametric (Section 4) methods, each with its own strengths and weaknesses (Kay, 1988; Pinna et al., 1996; Zhao and Gui, 2019). The choice of the method depends on the characteristics of the signal, the available data, and the specific requirements of the analysis, being often a trade-off between frequency resolution, variance reduction, and computational complexity.
2.3 Information-theoretic measures of coupling and causality
In this section, we present the well-known information-theoretic measures used for analyzing undirected and directed interactions in bivariate systems. Each of the measures is described with detail; the characterization of their mathematical relationships allows to highlight how they capture distinct aspects of statistical dependence.
2.3.1 Mutual information and mutual information rate
The most popular measure of coupling derived in the frame of information theoryis the mutual information (MI). The MI is a symmetric measure quantifying the amount of information shared by two random variables
where
where
Equation 10 establishes a direct and quantitative link between linear correlation and information-theoretic dependence. It is worth stressing that the MI, like the PCC, measures the static interaction between two random variables.
The mutual information rate (MIR) generalizes the MI between random variables by quantifying the dynamic coupling between the two stochastic processes
where
where
We anticipate that, in the case of stationary Gaussian processes, the MIR is closely connected to a well-known time-domain measure of non-directional dynamic coupling related to the concept of TD developed in the context of linear regression models (Geweke, 1982); the relevant derivations will be provided in Section 2.
2.3.2 Causal and instantaneous information transfer
Inferring directional interactions between time series is a fundamental task in the analysis of dynamical systems. Generally, the two random processes representing the dynamic activity of the units interact in a closed-loop manner, i.e., through bidirectional and reciprocal influences which allow to identify asymmetrical driver-response patterns (Porta and Faes, 2015).
In the field of information theory, a widely used measure for assessing such interactions is transfer entropy (TE), formally defined as (Schreiber, 2000):
where
Remarkably, the MIR can be formulated comparing the sum of the 2 TEs from
where
We remark that the TE is a well-known measure of directional information transfer related to the concept of Granger causality (GC) originally developed by Wiener (Wiener, 1956) and then made operative by Granger in the context of linear regression models (Granger, 1969), while the IT is a symmetric measure related to the concept of instantaneous causality (IC) (Chicharro, 2011).
3 Implementation through linear autoregressive models
This section presents the definition and practical implementation of the time, spectral and information-theoretic measures of directed and undirected coupling obtained through linear regression methods making use of univariate and bivariate autoregressive (AR) models. Linear AR models are ubiquitously used to assess dynamics and interactions in time series data, especially in the field of Network Physiology (Bressler and Seth, 2011; Seth et al., 2015; Porta and Faes, 2015; Faes et al., 2016b; Sparacino et al., 2024b; Vakitbilir et al., 2025). Here, we begin discussing three issues that have theoretical relevance and practical implications in the use of AR models for the computation of interaction measures.
The first observation is that fitting linear AR models on time series assumes linearity in the modelled interactions, but not in the processes to be analysed: indeed, while the model assumes linearity in its structure, this does not necessarily imply that the underlying time series must be linear (Barnett and Seth, 2023). Indeed, Wold’s decomposition theorem (Wold, 1938) guarantees that any stationary process can be decomposed into a linear model, although this model may be of infinite order and thus providing a non-parsimonious representation of an underlying nonlinear process (Hannan, 1979). Therefore, linear AR models may in principle be able to describe also the dynamics of processes with nonlinear generating mechanisms.
Another relevant observation is that, while linear AR models can be used to describe time series with any probability distribution, when the underlying processes are jointly Gaussian distributed the measures derived in the time domain (Barrett et al., 2010; Faes et al., 2016b) and in the spectral domain (Chicharro, 2011; Faes et al., 2021; Antonacci et al., 2021b; Sparacino et al., 2025a) have a striking information-theoretic interpretation. In fact, the parametric implementation exploits the knowledge that linear regression models capture all of the entropy differences relevant to the various information measures when the observed processes have a joint Gaussian distribution (Barrett et al., 2010; Faes et al., 2016b).
The third point regards the fact that linear AR models typically limit to past values only the possible influences of one process to another, thereby excluding instantaneous effects (i.e., effects occurring within the same lag) from the model structure (Lütkepohl, 2005). The consequence of this is that the model residuals (prediction errors) are correlated whenever instantaneous effects are present between the analysed time series. On the other hand, the absence of instantaneous effects, typically denoted as strict causality of the process (Korhonen et al., 1996; Baselli et al., 1997) implies that the covariance matrix of the residuals is diagonal. While strict causality is often assumed in the computation of causality measures, the presence of instantaneous effects has an impact on the derived measures. In the following subsections we will discuss such an impact and mention how bivariate measures coupling and causality measures can be corrected to account for instantaneous effects.
3.1 Formulation of linear parametric models of bivariate time series
The linear formulation leading to compute coupling measures requires identification of a bivariate AR model composed by two so-called full auto- and cross-regressive (ARX) models, from which restricted autoregressive (AR) models are derived to compute causality measures. Full ARX models feature two model equations, where the present states of the two processes are written as linear combinations of the past states of both processes weighted by a set of model coefficients plus the residuals. Assuming that
where
3.1.1 Model identification
The identification procedure of the ARX model in Equations 16a, b is typically performed by means of estimation methods based on minimizing the prediction error, i.e., the difference between actual and predicted data (Kay, 1988; Lütkepohl, 2005). While several approaches have been proposed throughout the years (Schlögl, 2006; Antonacci et al., 2020), the most common estimator is the multivariate version of the ordinary least-squares (OLS) method (Lütkepohl, 2005). Briefly, defining the past history of
As regards the selection of the model order
3.1.2 Restricted AR model
While the ARX model in Equations 16a,b provides a global representation of the overall bivariate process, to describe the linear interactions relevant to, e.g., the target process, we need to define a restricted AR model involving only
where
An issue with great practical relevance is that the order of the restricted model in Equation 17 is typically infinite and thus very difficult to identify from finite-length time series. The approach followed to face this issue in the context of causality analysis is essentially based on truncating the order of the restricted model to
3.2 Identification of restricted models
3.2.1 State-space models
The method based on SS models can be applied to the bivariate AR model in Equations 16a,b to derive the parameters of the two corresponding restricted AR models of
where
The parameters of the restricted model in Equations 19a,b are (
3.2.2 Resolution of the Yule-Walker equations
The issue related to the formation of AR restricted models from the ARX model in Equations 16a,b can be overcome also by solving the YW equations. The restricted model coefficients,
where
From Equation 21, the
can be expressed as
Then, once the covariance matrices
where in Equation 23 the covariance
To summarize, the above-described procedure is based first on computing the autocovariance sequence of the bivariate process
Contrary to the closed-form SS modeling approach presented in the previous subsection, the procedure described here is approximate because it retains the AR structure which has infinite order for the restricted model. The parameter determining the accuracy of the procedure is the number of lags used to truncate the past history of the process: considering the past up to lag
3.3 Time domain measures for linear processes
The parametric representation of the analysed bivariate process allows to derive measures of coupling and causality which are widely used for the description of symmetric and directed interactions in the time domain (Geweke, 1982; Bressler and Seth, 2011; Porta and Faes, 2015). These measures are obtained from the variances of the two analysed processes and of the prediction errors of the full and restricted models of Equations 16a,b, Equations 17. Specifically, a time-domain measure of the TD between the two random processes
The TD measure (Equation 25) is zero in the absence of any interaction between the two processes, resulting from a full equivalence between the bivariate AR description of
Equation 26 evidences evidences the two measures of Granger causality (GC) from
and GC from
in the case of strict causality (
3.4 Spectral measures for linear processes
In this section we present the tools whereby the linear parametric description of time series is widely exploited to describe coupling and causality in the frequency domain in a range of applicative fields, primarily including network neuroscience and network physiology (Schulz et al., 2013; Porta and Faes, 2015; Santiago-Fuentes et al., 2022; Sorelli et al., 2022; Jahani et al., 2025). To achieve a parametric estimation of the PSD matrix of the process (Equation 3), the ARX model in Equation 16 can be represented in the Z-domain through its Z-transforms yielding
Importantly, spectral factorization is the core of the causal analysis of dynamic processes studied in the frequency domain and, while it is ubiquitously performed using AR modeling, could actually be obtained regardless of it (Baccalá and Sameshima, 2022). As specified in Section 1.2, the PSD matrix
The bivariate interactions between the processes
where
where
can be interpreted as a measure of the influence of
Another line of research introduced independently frequency-domain measures of symmetric and directed interaction between two stationary jointly Gaussian processes based on the spectral expansion of the time-domain measures reviewed in Section 2.3) (Geweke, 1982; Ding et al., 2006; Chicharro, 2011). Given the spectral density matrix of the bivariate process, the frequency-specific measure of TD between
Moreover, exploiting the bivariate AR model and spectral factorization, Geweke formulated the so-called linear feedback measure defined as (Geweke, 1982)
which is non-negative and linked to the corresponding time domain GC measure (Equation 27) by the spectral integration property according to a relation similar to that of Equation 33:
The Geweke measure of spectral causality is an upper unbounded measure of GC which, if the bivariate process is strictly causal, can be related to the normalized measure of causal coherence. In fact, combining Equations 32, 34 one can easily show that the DC and the spectral GC are linked by the relation
Finally, the spectral measure of instantaneous causality (IC) was chosen ad hoc as (Geweke, 1982)
to satisfy the Geweke decomposition of the total dependence in the frequency domain, i.e.,
in such a way to be linked to the corresponding time domain IC measure (28) by the spectral integration property similarly to the relations established in Equations 33, 35 i.e.,
The spectral measure defined in Equation 36 to satisfy Equation 37 and to be related to the time-domain measure of instantaneous causality by Equation 38 does not fulfil all the requirements of Geweke, different from what occurs in the time domain. Indeed, it may be negative for some frequencies and has no clear physical meaning (Geweke, 1982). In the absence of instantaneous causality,
The issue of instantaneous causality in the computation of frequency domain measures of GC is a relevant one, and several efforts have been made to interpret instantaneous GC and to provide corrected measures (Faes and Nollo, 2010; Faes et al., 2013a; Nuzzi et al., 2021; Baccalá and Sameshima, 2021a). For instance, methods that identify a preferred direction for the instantaneous effects and then incorporate them together with lagged effects effects into directional measures of extended causality, were proposed by Faes and Nollo (2010) and Faes et al. (2013a): the methods exploit the Cholesky decomposition of the AR parameters and set the direction of zero-lag effects based on a-priori assumptions subjectively relying on physical knowledge (Faes and Nollo, 2010) or objectively relying on non-gaussianity of the AR residuals (Faes et al., 2013a). These methods were successfully applied to electroencephalographic rhythms (Faes et al., 2013a), as well as to cardiovascular and cerebrovascular oscillations (Pernice et al., 2022a). Measures which include instantaneous causality in the modelling approach are generally preferred because they enforce that zero-lag effects are ascribed to one of the two causal directions and therefore become zero both in time and frequency domain (Pernice et al., 2022a), essentially solving the issue about interpretability. Nevertheless, the assumptions about prior physiological knowledge or non-gaussianity of the residuals are not always satisfied, and therefore several alternatives based on keeping instantaneous effects as undirected but including them in extended spectral causality measures have been proposed to face the problem. As an example, Baccalá and Sameshima (2021a) discussed the theoretical interpretation of instantaneous GC within a spectral framework, and decomposed frequency-domain measures of causality, namely, directed transfer function and partial directed coherence, into lagged and instantaneous connectivity terms without the need of including the zero lag in AR models. On the other hand, Nuzzi et al. (2021) introduced an alternative frequency-domain decomposition of GC by obtaining a novel index of undirected instantaneous causality and a novel measure of GC including instantaneous effects, with the purpose to mitigate the confounding effect of zero-lag coupling. The issue of how it is best to treat instantaneous effects in the analysis of physiological interactions, e.g., cardiovascular interactions, where zero-lag interdependencies are expected to contribute significantly to the baroreflex mechanism (see, e.g., Faes et al. (2013a)), and of cardiorespiratory interactions, where the information transfer from respiration to heart rate variability is expected to be within-beat (Faes et al., 2012b), still remains an active area of research.
3.5 Connection between information-theoretic and spectral formulations
When formulated for jointly stationary Gaussian processes, the Geweke spectral and time domain measures of coupling and causality reviewed in the previous subsections have a straightforward information-theoretic interpretation (Geweke, 1982; Pernice et al., 2022b; Sparacino et al., 2024a). Indeed, the spectral measures of the bivariate interactions between two processes, defined by the spectral TD (Equation 6), the spectral GC (Equation 34) and the spectral IC (Equation 36), are closely related to the information-theoretic measures defined in Equations 11, 13, 15 by means of the spectral integration property (Geweke, 1982; Chicharro, 2011):
The spectral integration property is very important not only to connect the information-theoretic and spectral formulations of the interaction measures, but also to allow quantification of these measures with reference to specific oscillatory components contained within spectral bands of interest. Examples of band-specific integration of the spectral interaction measures to obtain values related to peculiar oscillations of a group of random processes are reported in the next sections for real-world systems.
4 Implementation through model-free approaches
The practical implementation of the information-theoretic measures of symmetric and directional coupling through model-free approaches assumes that the measures are estimated directly from data without assuming a parametric model for the underlying probability distribution. These approaches are especially useful in high-dimensional, non-Gaussian, or complex distributions where classical parametric methods fail. This section presents three widely used model-free approaches for estimating entropy-based measures of coupling and causality, i.e., the
4.1 Nearest-neighbour estimator
The
where
Besides the entropy of a scalar variable formulated as in Equation 41, the nearest neighbour estimator can be used to compute all of the entropy terms that compose a given coupling measure. However, as shown in Equation 13 for thr transfer entropy, the coupling and causality measures are expressed as combinations of entropy terms computed in spaces of different dimensions. Using the same nearest-neighbour search across these spaces leads to inconsistent distance scales, introducing estimation biases not canceled by entropy differences. To mitigate computational bias, the process begins by identifying the nearest neighbours within the full high-dimensional space, and then examining how these neighbours distribute across various lower-dimensional projections (Kraskov et al., 2004). Following this approach, given the bivariate system
where
where
with
where
From Equation 46, the IC measure and the MIR can be computed as:
The accuracy of entropy estimators can vary depending on both the data size and the chosen number of nearest neighbours (
4.1.1 Embedding procedures
Finding embedding vectors that adequately approximate the infinite-dimensional past states of the processes is a critical step in estimating information-theoretical measures using model-free approaches. When working with time series of finite length, e.g., the 300 samples typically used for the analysis of short-term physiological time series (Shaffer and Ginsberg, 2017), the employment of high-dimensional vectors to provide a more complete description of past processes leads to the curse of dimensionality and unreliable estimates of entropy quantities (Faes and Porta, 2014). A selection technique widely used in this frame is the uniform embedding approach, which simply uses a fixed number of equally spaced variables. Nevertheless, this method may overlook the most informative lags, potentially limiting the effectiveness of information-theoretic analyses in capturing relevant temporal dynamics (Kugiumtzis, 2013). An alternative approach was introduced to limit the size of the descriptive patterns and maximize their informational content about process dynamics, i.e., the non-uniform embedding approach introduced in (Faes et al., 2011; 2015a). In brief, a set of candidates including all possible states of the processes up to a maximum lag
4.2 Binning estimator
The binning estimation approach is based on performing uniform or non-uniform quantization of a continuous random variable and then estimating the entropy of the variable approximating probabilities with the frequency of visitation of the quantized states, or bins. Specifically, uniform quantization simplifies implementation by dividing the range of values into equal intervals (Faes and Porta, 2014), whereas non-uniform quantization better preserves the dynamic structure of data by adapting to its distribution (Darbellay and Vajda, 1999).
Let
The concepts outlined above extend naturally to multivariate cases, where quantization is performed independently on each scalar element of the analysed vector variable. Specifically, if we consider a
In the context of dynamic processes, the two stochastic processes
A key issue in implementing discretization methods is the selection of the free parameters of the estimator, i.e., the memory length
4.3 Permutation estimator
Permutation-based methods carry out symbolization by operating directly on discrete vector variables derived emphasizing the relative ordering of neighbouring sample amplitudes within each realization, rather than their specific absolute amplitude values (Bandt and Pompe, 2002). Given a general
It is worth noting that the permutation strategy is favoured when compared with the binning approach for the estimation of entropy from a limited number of observations of the variable under analysis since for the first the continuous
Analogously to the binning approach, estimation of the TE, presented in (Equation 13), requires that the relevant variables include either the past of the target process alone or combined with its present state, resulting in alphabet sizes of
For the permutation approach, the memory length
5 Practical computation of bivariate interaction measures
The practical computation of the information-theoretic and spectral measures of coupling and causality from two time series of
The software and the codes relevant to this work are collected in the BIM Matlab toolbox and available for free download from https://github.com/LauraSparacino.
5.1 Non-parametric estimation of the PSD
Spectral measures of coupling can be computed directly from the PSD terms of the set
A widely used non-parametric estimator of the PSD is the weighted covariance (WC) method (function bim_WCspectra.m). This estimator leverages the FT of the sample CCF of the observed data
where
where the asterisk denotes the complex conjugate. The definition in Equation 50 applies for
5.2 Linear autoregressive models
The linear ARX equation in Equations 16a,b is seen as a model of how the observed data have been generated, and an identification procedure (function bim_idARX.m) is applied after model order selection (function bim_mos_idARX.m) to provide estimates of the coefficients and innovation variances to be used for computing the coupling and causality measures in the information-theoretic and spectral domains. Then, computation of the information-theoretic measures of MIR, TE and IT amounts to identify restricted linear models through methods which extract the parameters of the restricted model from those of the full model (Section 2.2), i.e., based on (i) the resolution of the YW equations (function bim_MIRdec_lin_YW.m) or, equivalently, on (i) SS models (function bim_MIRdec_lin_SS.m). Side functions of (i) are bim_LinReg.m, which performs a linear regression of the present state of input target processes from the past states of input driver processes, and bim_Yule.m, which provides solution of the YW equations for a ARX process using discrete time Lyapunov equation; side functions of (ii) are bim_SSmodel.m, which computes the parameters of a SS model from those of a ARX model, and bim_submodel.m, which derives a submodel of a SS model. On the other hand, information-theoretic measures of coupling and causality can be obtained directly exploiting the spectral integration property (Section 2.4 and Section 2.5). If this is the case, spectral measures of TD, GC and IC are computed by first estimating the parametric PSD matrix of the set
5.3 Model-free approaches
Model-free estimation of the MIR, TE and IT measures can be performed by exploiting different approaches for the computation of entropy measures (Xiong et al., 2017; Azami et al., 2023). Regarding the approaches reviewed in this work, the KNN, binning and permutation estimators are implemented through the functions bim_MIRdec_KNN.m, bim_MIRdec_bin.m and bim_MIRdec_perm.m, respectively, taking as inputs the set
5.4 Assessment of statistical significance
This section presents the use of surrogate data analysis to statistically validate the proposed measures of coupling and causality in the information-theoretic and spectral domains. Validation is performed at the level of individual realizations of the observed random processes
The method of surrogate data (Theiler et al., 1992; Zhang, 2023) is employed to set a significance level for the coupling and causality measures. Specifically, to assess the significance of conditional mutual information measures (i.e.,
6 Exemplary applications to real-world time series
6.1 Cardiovascular interactions
In this section, we analyse physiological time series collected to study the effect of postural stress on cardiovascular variability (Faes et al., 2013c; Bari et al., 2016). One representative subject was selected for the following analyses, chosen from a dataset comprising healthy controls enrolled at the Neurology Division of Sacro Cuore Hospital, Negrar, Italy. Electrocardiogram (ECG) was acquired synchronously with arterial pressure (AP) measured at the level of middle finger through a photopletysmographic device (Finapres Medical Systems, Ohmenda, Netherlands) at a sampling rate of 1 kHz. From the raw signals, stationary time series of heart period (H) and systolic AP (S) were measured as detailed in (Faes et al., 2013c; Bari et al., 2016) during the supine resting state condition, and regarded as realizations of the H and S discrete-time processes, in turn assumed as uniformly sampled with a sampling frequency equal to the inverse of the mean heart period. The series, each of length equal to 251 beats, were preprocessed reducing the slow trends with an AR high-pass filter (zero phase; cut-off frequency 0.0156 Hz), removing the mean value and normalizing to unit variance.
Information and spectral measures of coupling (MIR/TD) and causality (TE/GC, IT/IC) were computed from the parameters of an ARX model (least squares estimation, model order set according to the AIC - maximum scanned model order: 8; selected model order: 6), restricted through resolution of the YW equations and represented in the frequency domain to get a parametric estimation of the PSD matrix. The mathematical derivations are presented in Section 2, while the practical computation is detailed in Section 4. The spectral profiles were integrated within two frequency bands of physiological interest, i.e., the low frequency (LF,
Figure 2a displays the spectral profiles of TD (
Figure 2. Cardiovascular signals show coherent oscillations in spectral bands with physiological meaning. (a) Red solid lines: spectral TD (
6.2 Case study in climate science
In this section, to showcase the use of the tools presented in this paper also outside the field of Network Physiology, we consider an exemplary case study in climate science, i.e., we investigate the interactions among the most representative indices descriptive of El Niño and the Southern Oscillation (ENSO). ENSO is a periodic fluctuation in the sea surface temperature and air pressure of the atmosphere overlying the equatorial Pacific Ocean, which is considered as the most prominent interannual climate variability on Earth (McPhaden et al., 2006). Since the exact initiating causes of an ENSO warm or cool events are not fully understood, it is important to analyze the statistical relationship between its two main components, i.e., atmospheric pressure and sea surface temperature. Such components are measured respectively by NINO34 (the East Central Tropical Pacific sea surface temperature anomaly, also called El Niño) and SOI (Southern Oscillation Index, the standardized difference in surface air pressure between Tahiti and Darwin), and are dynamically related to several other indexes that represent large scale climate patterns (Chang et al., 2003; Silini et al., 2023; Pinto et al., 2025c). The analyzed climate indices are taken from a public database (Silini et al., 2023), of which we consider the series SOI and NINO34 measured with a monthly sampling rate during the period 1950–2016 (792 data points) for which all time series values are available. The series were first detrended and deseasonalized.
Model-based and model-free information-theoretic measures of MIR, TE and IT were computed exploiting the linear parametric, KNN, binning and permutation approaches. Specifically, linear parametric measures were computed from the parameters of an ARX model (least squares estimation, model order set according to the AIC - maximum scanned model order: 12 (Faes et al., 2012a); selected model order: 10); restricted models were obtained via resolution of the YW equations (Section 2). The KNN estimator was implemented through the uniform embedding procedure, by fixing a maximum number of past samples in the embedding vectors of
Figure 3 summarizes the coupling and causality measures of MIR (
Figure 3. Different estimation approaches of coupling and causality measures suggest a bidirectional transfer of information in representative climate time series. The time domain MIR (
Overall, although the LIN, KNN, PERM and BIN estimators aim to quantify the same underlying information flow, their varying theoretical assumptions (continuous- or discrete-valued random variables), data manipulation steps (no transformation, discretization based on quantization or based on ordinal patterns), estimation approach (model-based vs. model-free), as well as their different sensitivity to data length, noise, and embedding parameters, explain why distinct numerical values may arise, even substantial as depicted in Figure 3. As a matter of fact, estimating information-theoretic measures such as transfer entropy or mutual information rate yields results that depend strongly on how probability distributions are inferred or system dynamics are modelled. Therefore, comparison between measures derived from different approaches should be avoided. Moreover, given an estimation approach, the parameter setting should be as much as possible uniform when comparing the same measure across different experimental conditions. In general, the selection of the appropriate estimator should be guided by the nature of the data, including its linearity, stationarity, noise characteristics, and available sample size.
7 Conclusion
This work provides a comprehensive review, theoretical description and practical implementation of the most popular time-domain, spectral and information-theoretic approaches for the investigation of both symmetrical and directional interactions in bivariate time series. Coupling and causality measures are described in their formulation, evaluated critically highlighting advantages and limitations, connected identifying their reciprocal relations, and showcased in exemplary applications in Network Physiology and Climate Science. Thanks to the freely available toolbox that practically implements the measures using model-based and model-free estimators, our groundwork provides researchers with a robust foundation for quantifying and interpreting several bivariate interdependencies across a wide range of applications.
The practical implementation of the coupling and causality measures through both model-based and model-free approaches allows a complete characterization of the complex interplay occurring in a variety of real-world scenarios. We show how parametric modelling offers interpretability and computational efficiency under the assumption of joint Gaussianity of the bivariate process analysed, and that fully model-free estimation techniques, including binning, permutation and nearest-neighbours estimators, achieve a non-linear description of the complex interdependencies among the data. Although inherently model-free, information-theoretic measures are herein contextualized through linear model-based interpretations, which enable frequency-specific insights into oscillatory dynamics.
The present work can thus serve as a driving force for future endeavours in the development and critical assessment of functional connectivity measure in bivariate systems, as well as help researchers to test such measures in a variety of applicative scenarios where the activity of dynamic systems is measured in terms of time series. Moreover, the systematic description and categorization of bivariate measures pursued in this work can pose solid basis to extend them to multivariate time series data, in contexts where more than two dynamic processes are simultaneously monitored. This approach is very popular in the field of Network Physiology, historically regarding the reconstruction of causal networks (Günther et al., 2022) where a range of extensions of the methods reviewed here has been proposed in the multivariate setting (Rosenberg et al., 1989; Baccalá and Sameshima, 2001; Faes et al., 2012b; Barnett and Seth, 2014; Montalto et al., 2014; Baccalá and Sameshima, 2021b; Baccalá and Sameshima, 2022), and more recently regarding the study of high-order interactions (Scagliarini et al., 2023) whereby collective interactions among three or more processes which cannot be reduced to pairwise dependencies are increasingly investigated extending tools for bivariate analysis (Faes et al., 2022; Scagliarini et al., 2023; Faes et al., 2025b; Sparacino et al., 2025b; Mijatovic et al., 2025; Faes et al., 2025a). These causal and high-order analyses of multivariate time series are closely connected (see, e.g., Stramaglia et al. (2024)), and their practical implementation implies to face similar issues to those tackled by the bivariate methods presented here, even though exacerbated by the need to work in higher-dimensional settings. In fact, as dimensionality increases, the joint probability space expands rapidly, raising theoretical constraints, computational demands and the risk of biased estimation, particularly with limited data. Up to now, while multivariate linear methods applied appear feasible across time, frequency and information-theoretic domains, truly multivariate non-parametric approaches to the study of causality networks and high-order interactions are scarce. The extension of the bivariate model-free methods reviewed here will have to face the theoretical and practical challenges posed by the curse of dimensionality, and is an open question for the ongoing research in the field.
Data availability statement
Publicly available datasets were analyzed in this study. This data can be found here: https://github.com/LauraSparacino.
Ethics statement
The studies involving humans were approved by Ethics Committee, Sacro Cuore Hospital, Negrar, Italy. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.
Author contributions
LS: Writing – original draft, Software, Investigation, Data curation, Visualization, Methodology, Validation, Formal Analysis. HP: Data curation, Formal Analysis, Visualization, Methodology, Software, Investigation, Writing – original draft. CB: Writing – review and editing, Methodology, Formal Analysis, Validation, Data curation, Software. YA: Validation, Formal Analysis, Methodology, Writing – review and editing, Investigation, Supervision. RP: Resources, Validation, Writing – review and editing, Supervision. AR: Supervision, Investigation, Writing – review and editing. LF: Methodology, Conceptualization, Investigation, Project administration, Supervision, Funding acquisition, Writing – review and editing.
Funding
The authors declare that financial support was received for the research and/or publication of this article. This research was supported by the project “HONEST - High-Order Dynamical Networks in Computational Neuroscience and Physiology: an Information-Theoretic Framework,” Italian Ministry of University and Research (funded by MUR, PRIN 2022; code 2022YMHNPY, CUP: B53D23003020006) and by European Union-NextGenerationEU - funds from Italian MUR, D.M. 737/2021 - EUROSTART 2021 research project “Novel Computational tools for Patient Stratification in cardiovascular diseases and brain disorders”. YA, RP, and LF were supported by SiciliAn MicronanOTecH Research And Innovation CEnter “SAMOTHRACE” (MUR, PNRR-M4C2, ECS_00000022), spoke 3–Università degli Studi di Palermo S2-COMMs–Micro and Nanotechnologies for Smart and Sustainable Communities. HP and AR were partially supported by CMUP, member of LASI, which is financed by national funds through Fundação para a Ciência e Tecnologia (FCT), under the project UID/00144/2025 (https://doi.org/10.54499/UID/00144/2025). HP thanks FCT, Portugal for the Ph.D. Grant 2022.11423.BD (https://doi.org/10.54499/2022.11423.BD).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors RP, APR, and LF declared that they were editorial board members of Frontiers at the time of submission. This had no impact on the peer review process and the final decision.
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The authors declare that no Generative AI was used in the creation of this manuscript.
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Keywords: correlation, causality, information dynamics, spectral integration property, parametric autoregressive models, network physiology
Citation: Sparacino L, Pinto H, Barà C, Antonacci Y, Pernice R, Rocha AP and Faes L (2026) Quantifying coupling and causality in dynamic bivariate systems: a unified framework for time-domain, spectral, and information-theoretic analysis. Front. Netw. Physiol. 5:1687132. doi: 10.3389/fnetp.2025.1687132
Received: 16 August 2025; Accepted: 13 November 2025;
Published: 06 January 2026.
Edited by:
Ulrich Parlitz, Max Planck Institute for Dynamics and Self-Organization, GermanyCopyright © 2026 Sparacino, Pinto, Barà, Antonacci, Pernice, Rocha and Faes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Luca Faes, bHVjYS5mYWVzQHVuaXBhLml0
†These authors have contributed equally to this work