The New Frontier of Network Physiology: Emerging Physiologic States in Health and Disease from Integrated Organ Network Interactions

An intriguing question in the new field of Network Physiology is how organ systems in the human body dynamically interact to coordinate functions, to maintain healthy homeostasis, and to generate distinct physiological states and behaviors at the organism level. Physiological systems exhibit complex dynamics, operate at different time scales and are regulated by multi-component mechanisms, which poses challenges to studying physiologic coupling and network interactions among systems with diverse dynamics. We present a conceptual framework and a method based on the concept of time delay stability to probe transient physiologic network interactions in a group of healthy subjects during sleep. We investigate the multi-layer network structure and dynamics of interactions among (i) physiologically relevant brain rhythms within and across cortical locations, (ii) brain rhythms and key peripheral organ systems, and (iii) the network structure and dynamics among peripheral organ systems across distinct physiological states. We demonstrate that each physiologic state (sleep stage) is characterized by a specific network structure and link strength distribution. The entire physiological network undergoes hierarchical reorganization across layers with the transition from one stage to another. Our findings are consistent across subjects and indicate a robust association of organ network structure and dynamics with physiologic state and function. The presented Network Physiology approach provides a new framework to explore physiologic states under health and disease through networks of organ interactions.