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Title: Global Sensitivity Analysis of High-Dimensional Neuroscience Models: An Example of Neurovascular Coupling
The complexity and size of state-of-the-art cell models have significantly increased in part due to the requirement that these models possess complex cellular functions which are thought—but not necessarily proven—to be important. Modern cell mod- els often involve hundreds of parameters; the values of these parameters come, more often than not, from animal experiments whose relationship to the human physiology is weak with very little information on the errors in these measurements. The concomi- tant uncertainties in parameter values result in uncertainties in the model outputs or quantities of interest (QoIs). Global sensitivity analysis (GSA) aims at apportioning to individual parameters (or sets of parameters) their relative contribution to output uncer- tainty thereby introducing a measure of influence or importance of said parameters. New GSA approaches are required to deal with increased model size and complexity; a three-stage methodology consisting of screening (dimension reduction), surrogate modeling, and computing Sobol’ indices, is presented. The methodology is used to analyze a physiologically validated numerical model of neurovascular coupling which possess 160 uncertain parameters. The sensitivity analysis investigates three quantities of interest, the average value of K+ in the extracellular space, the average volumetric flow rate through the perfusing vessel, and the minimum value of the actin/myosin complex in the smooth muscle cell. GSA provides a measure of the influence of each parameter, for each of the three QoIs, giving insight into areas of possible physiological dysfunction and areas of further investigation.  more » « less
Award ID(s):
1745654
NSF-PAR ID:
10104988
Author(s) / Creator(s):
Date Published:
Journal Name:
Bulletin of mathematical biology
Volume:
81
ISSN:
1522-9602
Page Range / eLocation ID:
1805-1828
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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