title: Inferring pathological states in cortical neuron microcircuits.
abstract: The brain activity is to a large extent determined by states of neural cortex microcircuits. Unfortunately, accuracy of results from neural circuits׳ mathematical models is often biased by the presence of uncertainties in underlying experimental data. Moreover, due to problems with uncertainties identification in a multidimensional parameters space, it is almost impossible to classify states of the neural cortex, which correspond to a particular set of the parameters. Here, we develop a complete methodology for determining uncertainties and the novel protocol for classifying all states in any neuroinformatic model. Further, we test this protocol on the mathematical, nonlinear model of such a microcircuit developed by Giugliano et al. (2008) and applied in the experimental data analysis of Huntington׳s disease. Up to now, the link between parameter domains in the mathematical model of Huntington׳s disease and the pathological states in cortical microcircuits has remained unclear. In this paper we precisely identify all the uncertainties, the most crucial input parameters and domains that drive the system into an unhealthy state. The scheme proposed here is general and can be easily applied to other mathematical models of biological phenomena.
authors.affiliation: Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun, Poland. Electronic address: jr@fizyka.umk.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Rydzewski
authors.affiliation: Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun, Poland. Electronic address: wiesiek@fizyka.umk.pl.
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Nowak
authors.affiliation: Department of Mathematics and Computer Science, University of Catania, Viale A. Doria, 6-95125 Catania, Italy. Electronic address: nicosia@dmi.unict.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nicosia
mesh_terms: D000465:Algorithms; D002540:Cerebral Cortex / Q000473:pathology*; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013269:Stochastic Processes
keywords: Clustering; Cortical neuron microcircuit; Neuroinformatics; Ordinary differential equations model; Sensitivity analysis