Winter2017 - Brain Energy Metabolism with PPP

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Short description
Winter2017 - Brain Energy Metabolism with PPP

This model is described in the article:

Felix Winter1,2, Catrin Bludszuweit-Philipp1 and Olaf Wolkenhauer2,3
Journal of Cerebral Blood Flow & Metabolism

Abstract:

Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) is a standard clinical tool for the detection of brain activation. In Alzheimer’s disease (AD), task-related and resting state fMRI have been used to detect brain dysfunction. It has been shown that the shape of the BOLD response is affected in early AD. To correctly interpret these changes, the mechanisms responsible for the observed behaviour need to be known. The parameters of the canonical hemodynamic response function (HRF) commonly used in the analysis of fMRI data have no direct biological interpretation and cannot be used to answer this question. We here present a model that allows relating AD-specific changes in the BOLD shape to changes in the underlying energy metabolism. According to our findings, the classic view that differences in the BOLD shape are only attributed to changes in strength and duration of the stimulus does not hold. Instead, peak height, peak timing and full width at half maximum are sensitive to changes in the reaction rate of several metabolic reactions. Our systems-theoretic approach allows the use of patient-specific clinical data to predict dementia- driven changes in the HRF, which can be used to improve the results of fMRI analyses in AD patients.

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Format
SBML (L2V3)
Related Publication
  • Mathematical analysis of the influence of brain metabolism on the BOLD signal in Alzheimer's disease
  • Felix Winter1, 2, Catrin Bludszuweit-Philipp1 and Olaf Wolkenhauer2, 3
  • Journal of Cerebral Blood Flow & Metabolism
  • 1ASD Advanced Simulation and Design GmbH, Rostock, Germany 2Department of Systems Biology and Bioinformatics, Rostock University, Rostock, Germany 3Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa
  • Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) is a standard clinical tool for the detection of brain activation. In Alzheimer’s disease (AD), task-related and resting state fMRI have been used to detect brain dysfunction. It has been shown that the shape of the BOLD response is affected in early AD. To correctly interpret these changes, the mechanisms responsible for the observed behaviour need to be known. The parameters of the canonical hemodynamic response function (HRF) commonly used in the analysis of fMRI data have no direct biological interpretation and cannot be used to answer this question. We here present a model that allows relating AD-specific changes in the BOLD shape to changes in the underlying energy metabolism. According to our findings, the classic view that differences in the BOLD shape are only attributed to changes in strength and duration of the stimulus does not hold. Instead, peak height, peak timing and full width at half maximum are sensitive to changes in the reaction rate of several metabolic reactions. Our systems-theoretic approach allows the use of patient-specific clinical data to predict dementia- driven changes in the HRF, which can be used to improve the results of fMRI analyses in AD patients.
Contributors
Felix Winter

Metadata information

is
BioModels Database MODEL1603240000
BioModels Database BIOMD0000000627
isDerivedFrom
BioModels Database MODEL1411210000
BioModels Database BIOMD0000000554
978-1-4613-1161-4
hasTaxon
Taxonomy Homo sapiens
hasPart
Gene Ontology tricarboxylic acid cycle
Gene Ontology pentose-phosphate shunt
Gene Ontology oxidative phosphorylation
Gene Ontology glycolytic process
isDescribedBy
hasProperty
Human Disease Ontology Alzheimer's disease
Mathematical Modelling Ontology Ordinary differential equation model
occursIn
Brenda Tissue Ontology brain
Curation status
Curated
  • Model originally submitted by : Felix Winter
  • Submitted: 24-Mar-2016 20:58:10
  • Last Modified: 07-Apr-2017 18:55:35
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 07-Apr-2017 18:55:35
    • Submitted by: Felix Winter
    • With comment: Current version of Winter2017 - Brain Energy Metabolism with PPP
  • Version: 1 public model Download this version
    • Submitted on: 24-Mar-2016 20:58:10
    • Submitted by: Felix Winter
    • With comment: Original import of Winter2016_Brain_Energy_Metabolism_with_PPP
Curator's comment:
(added: 13 Mar 2017, 12:24:25, updated: 13 Mar 2017, 12:24:25)
Figure 3 of the reference publication has been reproduced here. The model was simulated using Copasi, and the plots were generated using Gnuplot. To import the SBML model in Copasi without any issues, the latest development version (atleast Build 144) is needed. The SED-ML and Copasi file to reproduce the above figure can be accessed from the below link.