Tomislav Stankovski

Inference of time-evolving coupled dynamical systems in the presence of noise.

A new method is introduced for analysis of interactions between time-dependent coupled oscillators, based on the signals they generate. It distinguishes unsynchronized dynamics from noise-induced phase slips and enables the evolution of the coupling functions and other parameters to be followed. It is based on phase dynamics, with Bayesian inference of the time-evolving parameters achieved by shaping the prior densities to incorporate knowledge of previous samples. The method is tested numerically and applied to reveal and quantify the time-varying nature of cardiorespiratory interactions.

Evolution of cardiorespiratory interactions with age

We describe an analysis of cardiac and respiratory time series recorded from 189 subjects of both genders aged 16–90. By application of the synchrosqueezed wavelet transform, we extract the respiratory and cardiac frequencies and phases with better time resolution than is possible with the marked events procedure. By treating the heart and respiration as coupled oscillators, we then apply a method based on Bayesian inference to find the underlying coupling parameters and their time dependence, deriving from them measures such as synchronization, coupling directionality and the relative contributions of different mechanisms. We report a detailed analysis of the reconstructed cardiorespiratory coupling function, its time evolution and age dependence. We show that the direct and indirect respiratory modulations of the heart rate both decrease with age, and that the cardiorespiratory coupling becomes less stable and more time-variable.

Coupling functions in networks of oscillators

Networks of interacting oscillators abound in nature, and one of the prevailing challenges in science is how to characterize and reconstruct them from measured data. We present a method of reconstruction based on dynamical Bayesian inference that is capable of detecting the effective phase connectivity within networks of time-evolving coupled phase oscillators subject to noise. It not only reconstructs pairwise, but also encompasses couplings of higher degree, including triplets and quadruplets of interacting oscillators. Thus inference of a multivariate network enables one to reconstruct the coupling functions that specify possible causal interactions, together with the functional mechanisms that underlie them. The characteristic features of the method are illustrated by the analysis of a numerically generated example: a network of noisy phase oscillators with time-dependent coupling parameters. To demonstrate its potential, the method is also applied to neuronal coupling functions from single- and multi-channel electroencephalograph recordings. The cross-frequency δ, α to α coupling function, and the θ, α, γ to γ triplet are computed, and their coupling strengths, forms of coupling function, and predominant coupling components, are analysed. The results demonstrate the applicability of the method to multivariate networks of oscillators, quite generally.

Dynamical Bayesian inference of time-evolving interactions: From a pair of coupled oscillators to networks of oscillators

Living systems have time-evolving interactions that, until recently, could not be identified accurately from recorded time series in the presence of noise. Stankovski et al. [Phys. Rev. Lett. 109, 024101 (2012)] introduced a method based on dynamical Bayesian inference that facilitates the simultaneous detection of time-varying synchronization, directionality of influence, and coupling functions. It can distinguish unsynchronized dynamics from noise-induced phase slips. The method is based on phase dynamics, with Bayesian inference of the time-evolving parameters being achieved by shaping the prior densities to incorporate knowledge of previous samples. We now present the method in detail using numerically generated data, data from an analog electronic circuit, and cardiorespiratory data. We also generalize the method to encompass networks of interacting oscillators and thus demonstrate its applicability to small-scale networks.

Coupling functions: Universal insights into dynamical interaction mechanisms

The dynamical systems found in Nature are rarely isolated. Instead they interact and influence each other. The coupling functions that connect them contain detailed information about the functional mechanisms underlying the interactions and prescribe the physical rule specifying how an interaction occurs. Here, we aim to present a coherent and comprehensive review encompassing the rapid progress made recently in the analysis, understanding and applications of coupling functions. The basic concepts and characteristics of coupling functions are presented through demonstrative examples of different domains, revealing the mechanisms and emphasizing their multivariate nature. The theory of coupling functions is discussed through gradually increasing complexity from strong and weak interactions to globally-coupled systems and networks. A variety of methods that have been developed for the detection and reconstruction of coupling functions from measured data is described. These methods are based on different statistical techniques for dynamical inference. Stemming from physics, such methods are being applied in diverse areas of science and technology, including chemistry, biology, physiology, neuroscience, social sciences, mechanics and secure communications. This breadth of application illustrates the universality of coupling functions for studying the interaction mechanisms of coupled dynamical systems.

Time-frequency methods and voluntary ramped-frequency breathing: A powerful combination for exploration of human neurophysiological mechanisms

We experimentally altered the timing of respiratory motoneuron activity as a means to modulate and better understand otherwise hidden human central neural and hemodynamic oscillatory mechanisms. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations, and muscle sympathetic nerve activity in 13 healthy supine young men who gradually increased or decreased their breathing frequencies between 0.05 and 0.25 Hz over 9-min periods. We analyzed results with traditional time- and frequency-domain methods, and also with time-frequency methods (wavelet transform, wavelet phase coherence, and directional coupling). We determined statistical significance and identified frequency boundaries by comparing measurements with randomly generated surrogates. Our results support several major conclusions. First, respiration causally modulates both sympathetic (weakly) and vagal motoneuron (strongly) oscillations over a wide frequency range-one that extends well below the frequency of actual breaths. Second, breathing frequency broadly modulates vagal baroreflex gain, with peak gains registered in the low frequency range. Third, breathing frequency does not influence median levels of sympathetic or vagal activity over time. Fourth, phase relations between arterial pressure and sympathetic and vagal motoneurons are unaffected by breathing, and are therefore likely secondary to intrinsic responsiveness of these motoneurons to other synaptic inputs. Finally, breathing frequency does not affect phase coherence between diastolic pressure and muscle sympathetic oscillations, but it augments phase coherence between systolic pressure and R-R interval oscillations over a limited portion of the usual breathing frequency range. These results refine understanding of autonomic oscillatory processes and those physiological mechanisms known as the human respiratory gate.

Alterations in the coupling functions between cortical and cardio-respiratory oscillations due to anaesthesia with propofol and sevoflurane.

The precise mechanisms underlying general anaesthesia pose important and still open questions. To address them, we have studied anaesthesia induced by the widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics, computing cross-frequency coupling functions between neuronal, cardiac and respiratory oscillations in order to determine their mutual interactions. The phase domain coupling function reveals the form of the function defining the mechanism of an interaction, as well as its coupling strength. Using a method based on dynamical Bayesian inference, we have thus identified and analysed the coupling functions for six relationships. By quantitative assessment of the forms and strengths of the couplings, we have revealed how these relationships are altered by anaesthesia, also showing that some of them are differently affected by propofol and sevoflurane. These findings, together with the novel coupling function analysis, offer a new direction in the assessment of general anaesthesia and neurophysiological interactions, in general.

The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study

Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; non‐invasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non‐linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone.

A tutorial on time-evolving dynamical Bayesian inference

In view of the current availability and variety of measured data, there is an increasing demand for powerful signal processing tools that can cope successfully with the associated problems that often arise when data are being analysed. In practice many of the data-generating systems are not only time-variable, but also influenced by neighbouring systems and subject to random fluctuations (noise) from their environments. To encompass problems of this kind, we present a tutorial about the dynamical Bayesian inference of time-evolving coupled systems in the presence of noise. It includes the necessary theoretical description and the algorithms for its implementation. For general programming purposes, a pseudocode description is also given. Examples based on coupled phase and limit-cycle oscillators illustrate the salient features of phase dynamics inference. State domain inference is illustrated with an example of coupled chaotic oscillators. The applicability of the latter example to secure communications based on the modulation of coupling functions is outlined. MatLab codes for implementation of the method, as well as for the explicit examples, accompany the tutorial.

Neural Cross-Frequency Coupling Functions

Although neural interactions are usually characterized only by their coupling strength and directionality, there is often a need to go beyond this by establishing the functional mechanisms of the interaction. We introduce the use of dynamical Bayesian inference for estimation of the coupling functions of neural oscillations in the presence of noise. By grouping the partial functional contributions, the coupling is decomposed into its functional components and its most important characteristics—strength and form—are quantified. The method is applied to characterize the δ-to-α phase-to-phase neural coupling functions from electroencephalographic (EEG) data of the human resting state, and the differences that arise when the eyes are either open (EO) or closed (EC) are evaluated. The δ-to-α phase-to-phase coupling functions were reconstructed, quantified, compared, and followed as they evolved in time. Using phase-shuffled surrogates to test for significance, we show how the strength of the direct coupling, and the similarity and variability of the coupling functions, characterize the EO and EC states for different regions of the brain. We confirm an earlier observation that the direct coupling is stronger during EC, and we show for the first time that the coupling function is significantly less variable. Given the current understanding of the effects of e.g., aging and dementia on δ-waves, as well as the effect of cognitive and emotional tasks on α-waves, one may expect that new insights into the neural mechanisms underlying certain diseases will be obtained from studies of coupling functions. In principle, any pair of coupled oscillations could be studied in the same way as those shown here.