Keck Laboratory for Network Physiology - Network Physiology: mapping interactions between physiologic organ systems

Network Physiology: mapping interactions between physiologic organ systems

In contrast to the unorthodox diagnostic approaches of the fictional character Dr. Gregory House from the acclaimed US TV-series “House” who, in a detective-like manner, considers a variety of interactions between multiple physiologic systems and variables to understand origins of symptoms in order to reach the right diagnosis, health care specialists traditionally focus on a single physiological system. Cardiologists mainly examine the heart and consider ECG signals; pulmonologists check lung structure and function and probe respiratory patterns; and brain neurologists study EEG. However, the human organism is an integrated network of interconnected and interacting physiologic organ systems, where each system is a multi-component structural and regulatory network. The complex behavior of one physiological system may be affected by changes in the dynamics of other systems in the physiologic network of organ networks. Due to these interactions, failure of one system may trigger a breakdown of the entire physiologic network.

Multiple organ failure, a leading cause of death in intensive care units, is a manifestation of such a breakdown. Yet, despite its importance, the network of interactions between diverse integrated organ systems is not known. Identifying and quantifying the network of physiologic interactions is a major challenge. The structural and neuronal networks that control physiological systems lead to a high degree of complexity characterized by intermittent, scale-invariant and nonlinear behaviors, which require modern statistical physics, mathematical and computational approaches. This complexity is further compounded by various coupling and feedback interactions that continuously vary in time, and the nature of which is not understood. Currently, there is no adequate theoretical framework and computational technology to probe this level of complexity. To address these problems, there is a clear need for a new field to fuse research in physiology with modern approaches derived from statistical and computational physics and the theory of complex networks.

We utilize large-scale physiological databases of multi-channel recordings from key physiological systems over multiple hours/days from hundreds of subjects, as well as analytic and modeling approaches based on novel concepts, including phase synchronization and time delay stability, to probe the network of coupling between organ systems. This will have far-reaching implications in improving clinical diagnosis and in assessment of comprehensive effects of pharmacological treatments aimed at specific organs that may adversely affect links to other systems.

In our pilot empirical study (Nature Comm. 3:702, Feb 2012), we proposed an approach to identify a network of dynamic interactions among the cerebral, cardiac, respiratory, ocular and locomotor systems. We found that different physiologic states (e.g., light or deep sleep) are characterized by a distinct network structure. Our system-wide integrative approach has generated great interest in the community (Science News, Sept 22, 2012), and has initiated a new field, Network Physiology, as evidenced by the Harvard Catalyst symposium (Cambridge, Oct, 2012) and the special issue in New Journal of Physics (Sept, 2013) on Network Physiology.

The unique fundamental question we address will change the current paradigm of defining health and physiologic states by shifting the focus from single organ systems to the network of organ interactions. Our investigations will unravel the mystery of how health emerges as a result of organ interactions. This program will establish basic principles of organ integration that generate emergent behavior of the human body as a single entity able to adapt to internal and external perturbations.

The outcome of this project will: (i) revolutionize our knowledge and understanding of the fundamental mechanisms that regulate and coordinate organ-to-organ interactions; (ii) establish first quantitative measures of the interactions between diverse organ systems and of their collective network behavior; (iii) uncover relations between physiologic states and patterns of organ network interactions; and thereby (iv) will catalyze the development of an entirely new field of interdisciplinary research, Network Physiology.

Related Publications:

Book Chapters:

Ivanov PCh and Bartsch RP.

Network Physiology: Mapping Interactions Between Networks of Physiologic Networks. [ PDF ]

In "Networks of Networks: the last Frontier of Complexity", edited by D'Agostino G and Scala A. Springer International Publishing Switzerland, Series Title 5394; 2014: pp. 203-222

Ivanov PCh, Liu KKL, Lin A and Bartsch RP.

Network Physiology: From Neural Plasticity to Organ Network Interactions. [ PDF ]

in "Emergent Complexity from Nonlinearity, in Physics, Engineering and the Life Sciences",

edited by Mantica G, Stoop R, and Stramaglia S.

Springer Proceedings in Physics 191

Pages 145-165 Published: 2017

Peer-Reviewed Articles and Conference Proceedings:

Ivanov PCh, Liu KKL, and Bartsch RP.

Focus on the emerging new fields of network physiology and network medicine. [ PDF ]

New Journal of Physics, 2016; 18:100201.

Moorman J. R., Lake D. E., and Ivanov PCh.

Early Detection of Sepsis—A Role for Network Physiology? [ PDF ]