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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 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. 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 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. 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. 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 assessment of causality, isolation and autonomy opens new perspectives for the analysis of coupled biological processes in both physiological and clinical investigations.

While the standard network description of complex systems is based on quantifying links between pairs of system units, higher-order interactions (HOIs) involving three or more units play a major role in governing the collective network behavior. This work introduces an 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 propose a framework to decompose it into measures quantifying Granger-causal and instantaneous influences, as well as to expand it in the frequency domain. The framework exploits the spectral representation of vector autoregressive and state-space models to assess synergistic and redundant interactions among groups of processes, both in specific bands and in the time domain after whole-band integration. Validation on simulated networks illustrates how the spectral OIR can highlight redundant and synergistic HOIs emerging at specific frequencies but not using time-domain measures. The application to physiological networks described by heart period, arterial pressure and respiration measured in healthy subjects during paced breathing, and to brain networks described by ECoG 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 of autonomic control and altered consciousness. The proposed framework allows a hierarchically-organized evaluation of time- and frequency-domain interactions in networks mapped by multivariate time series, and its high flexibility and scalability make it suitable to investigate networks beyond pairwise interactions in neuroscience, physiology and other fields.

Despite the widespread diffusion of nonlinear methods for heart rate variability (HRV) analysis, the presence and the extent to which nonlinear dynamics contribute to short-term HRV is still controversial. This work aims at testing the hypothesis that different types of nonlinearity can be observed in HRV depending on the method adopted and on the physiopathological state. Two entropy-based measures of time series complexity (normalized complexity index, NCI) and regularity (information storage, IS), and a measure quantifying deviations from linear correlations in a time series (Gaussian linear contrast, GLC), are applied to short HRV recordings obtained in young (Y) and old (O) healthy subjects and in myocardial infarction (MI) patients monitored in the resting supine position and in the upright position reached through head-up tilt. The method of surrogate data is employed to detect the presence of and quantify the contribution of nonlinear dynamics to HRV. We find that the three measures differ both in their variations across groups and conditions and in the number and strength of nonlinear HRV dynamics detected: at rest, IS reveals a significantly lower number of nonlinear dynamics in Y, whereas during tilt GLC reveals significantly stronger nonlinear HRV dynamics in MI; in the transition from rest to tilt, all measures detect a significant weakening of nonlinear HRV dynamics in Y, while only GLC detects a significant strengthening of such dynamics in MI. These results suggest that distinct dynamic structures, detected with different sensitivity by nonlinear measures, lie beneath short-term HRV in different physiological states and pathological conditions.