Document Type

Article

Source Publication Title

PLOS Computational Biology

DOI

http://dx.doi.org/10.1371/journal.pcbi.1005261

Abstract

Using a model for the dynamics of the full somatic nervous system of the nematode C. elegans, we address how biological network architectures and their functionality are degraded in the presence of focal axonal swellings (FAS) arising from neurodegenerative disease and/or traumatic brain injury. Using biophysically measured FAS distributions and swelling sizes, we are able to simulate the effects of injuries on the neural dynamics of C. elegans, showing how damaging the network degrades its low-dimensional dynamical responses. We visualize these injured neural dynamics by mapping them onto the worm’s low-dimensional postures, i.e. eigenworm modes. We show that a diversity of functional deficits arise from the same level of injury on a connectomic network. Functional deficits are quantified using a statistical shape analysis, a procrustes analysis, for deformations of the limit cycles that characterize key behaviors such as forward crawling. This procrustes metric carries information on the functional outcome of injuries in the model. Furthermore, we apply classification trees to relate injury structure to the behavioral outcome. This makes testable pre- dictions for the structure of an injury given a defined functional deficit. More critically, this study demonstrates the potential role of computational simulation studies in understanding how neuronal networks process biological signals, and how this processing is impacted by network injury. [©2017Kunertet al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproductionin any medium, providedthe original author and sourceare credited. DOI: https://doi.org/10.1371/journal.pcbi.1005261]

Disciplines

Mathematics | Physical Sciences and Mathematics

Publication Date

1-5-2017

Language

English

Included in

Mathematics Commons

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