The Human Organism as an Integrated Interaction Network: Recent Conceptual and Methodological Challenges

Abstract

The field of Network Physiology aims to advance our understanding of how physiological systems and sub-systems interact to generate a variety of behaviors and distinct physiological states, to optimize the organism's functioning, and to maintain health. Within this framework, which considers the human organism as an integrated network, vertices are associated with organs while edges represent time-varying interactions between vertices. Likewise, vertices may represent networks on smaller spatial scales leading to a complex mixture of interacting homogeneous and inhomogeneous networks of networks. Lacking adequate analytic tools and a theoretical framework to probe interactions within and among diverse physiological systems, current approaches focus on inferring properties of time-varying interactions—namely strength, direction, and functional form—from time-locked recordings of physiological observables. To this end, a variety of bivariate or, in general, multivariate time-series-analysis techniques, which are derived from diverse mathematical and physical concepts, are employed and the resulting time-dependent networks can then be further characterized with methods from network theory. Despite the many promising new developments, there are still problems that evade from a satisfactory solution. Here we address several important challenges that could aid in finding new perspectives and inspire the development of theoretic and analytical concepts to deal with these challenges and in studying the complex interactions between physiological systems.

Measuring the Rate of Information Exchange in Point-Process Data With Application to Cardiovascular Variability

“…The proposed approach to estimate MIR in the presence of short and possibly noisy point process data is recommended for applications in the field of Network Physiology, where the estimation of organ system interactions is typically challenged by the inherently complex nature of human physiological signals (Lehnertz et al, 2020). In our work, where complex point process interactions between the heartbeat timings and the arrival times of the sphygmic wave on the body periphery have been analyzed, we detected significant coupling between the two processes in all subjects and experimental conditions.…”

Health and Disease Are Dynamic Complex-Adaptive States Implications for Practice and Research

“…The higher-level external environment provides the necessary information to the lower levels that constrain their emergent possibilities, and thereby all them to "do the work" required to maintain life and health. The latter is particularly evident from network physiology research (36,54,55). For completeness the figure integrates the network relationships between the layers, as well as the main HPA-axis regulatory pathways.…”

“…Importantly, while we understand HPA axis regulation and while we have a fairly detailed understanding of its regulatory pathways, it remains yet unclear how the underlying various low-level physiological networks work in detail, and how they interact with each other (54). However, while these "microscopic" physiological details are missing, they are not always necessary to appreciate their observable "macroscopic" consequences (36).…”

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

“…By understanding the bigger picture, it allows, on the one hand, the detection of potential drug targets, while at the same time offering the possibility of a systems approach to diagnosis and therapy ( 21 , 27 , 31 , 32 ). Furthermore, under the framework of the recently emerging field of network physiology, network approaches have proven valuable to describe the structural organization and functional interrelations between different physiological and organ systems on the whole-organism level ( 18 , 22 , 33 – 35 ). Noteworthy, in the last decade perhaps the most remarkable breakthroughs of complex network analysis were achieved in neuronal physiology, where these approaches are used to quantify the brain’s functional and anatomical organization and have reached the maturity to be translated into clinical practice ( 36 – 39 ).…”