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Fractal Regulatory Function of the Circadian System


One ofthe most puzzling phenomena in modern physiology is the existence of fractal patterns in a wide range of physiological systems (i.e., the structure of fluctuations are similar at different time scales), which challenges the traditional theory of homeostasis of maintaining physiologic constancy The physiological importance of fractal control is demonstrated In numerous studies and exemplified by reduced fractal cardiac and activity controls with aging and under pathological conditions, and most importantly, by the predictive value of reduced fractal cardiac control for decreased survival.. Despite the clear importance of fractal phenomena, to date, no underlying mechanism has been established for fractal control in any neural or physiological system. The Pi's recent studies indicate that the circadian system is critically involved in the fractal control of motor activity at multiple time scales. The proposal will formally assess the physiological significance and the neurobiological basis ofthe fractal regulatory function ofthe circadian system. The primary goal is to identify the neuronal nodes and pathways through which the circadian system imparts fractal activity control. During the previous 2-year mentored phase, PI and his colleagues have completed the analyses to reveal the effects of changes in the central circadian system on fractal activity control (the originally proposed Specific Aim 1). New results provided first direct evidence that dysfunction ofthe central circadian pacemaker leads to reduced fractal activity control in humans. The subsequent three years of the independent research phase will allow the PI to achieve the main research goal and help establish the PI as an independent researcher in the field. The specific aims are 1) to determine the effects of circadian misalignment on fractal activity control; and 2) to identify and validate neuronal node(s) in the activity control network and their interactions that contribute to fractal activity control. Achieving these aims will provide the neurophysiologic basis forthe first model of fractal control. Better understanding ofthe neuronal circuitry involving in circadian and activity regulation ought to provide useful guidance for improved diagnosis and treatment of circadian-related sleep and behavioral disturbances.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.