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.

Agency
National Institute of Health (NIH)
Type
Research Transition Award (R00)
Project #
5R00HL102241-05
Application #
8646975
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Laposky, Aaron D
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin et al. (2016) Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation. Front Physiol 7:174
Holmes, Matthew L; Manor, Brad; Hsieh, Wan-hsin et al. (2016) Tai Chi training reduced coupling between respiration and postural control. Neurosci Lett 610:60-5
Hu, Kun; Riemersma-van der Lek, Rixt F; Patxot, Melissa et al. (2016) Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial. Sci Rep 6:27742
Yeh, Chien-Hung; Hung, Chi-Yao; Wang, Yung-Hung et al. (2016) Novel application of a Wii remote to measure spasticity with the pendulum test: Proof of concept. Gait Posture 43:70-5
Lin, Chen; Chang, Yi-Chung; Cheng, Ya-Chen et al. (2016) Probing the Fractal Pattern of Heartbeats in Drosophila Pupae by Visible Optical Recording System. Sci Rep 6:31950
Yeh, Chien-Hung; Lo, Men-Tzung; Hu, Kun (2016) Spurious cross-frequency amplitude-amplitude coupling in nonstationary, nonlinear signals. Physica A 454:143-150
Chen, Michael C; Chiang, Wei-Yin; Yugay, Tatiana et al. (2016) Anterior Insula Regulates Multiscale Temporal Organization of Sleep and Wake Activity. J Biol Rhythms 31:182-93
Morris, Christopher J; Purvis, Taylor E; Hu, Kun et al. (2016) Circadian misalignment increases cardiovascular disease risk factors in humans. Proc Natl Acad Sci U S A 113:E1402-11
Lo, Men-Tzung; Chang, Yi-Chung; Lin, Chen et al. (2015) Outlier-resilient complexity analysis of heartbeat dynamics. Sci Rep 5:8836
Wang, Joshua L; Lim, Andrew S; Chiang, Wei-Yin et al. (2015) Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans. Ann Neurol 78:317-22

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