Mechanistic model for human brain metabolism and its connection to the neurovascular coupling
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Published:2022-12-22
Issue:12
Volume:18
Page:e1010798
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ISSN:1553-7358
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Container-title:PLOS Computational Biology
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language:en
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Short-container-title:PLoS Comput Biol
Author:
Sundqvist NicolasORCID,
Sten Sebastian,
Thompson PeterORCID,
Andersson Benjamin Jan,
Engström Maria,
Cedersund GunnarORCID
Abstract
The neurovascular and neurometabolic couplings (NVC and NMC) connect cerebral activity, blood flow, and metabolism. This interconnection is used in for instance functional imaging, which analyses the blood-oxygen-dependent (BOLD) signal. The mechanisms underlying the NVC are complex, which warrants a model-based analysis of data. We have previously developed a mechanistically detailed model for the NVC, and others have proposed detailed models for cerebral metabolism. However, existing metabolic models are still not fully utilizing available magnetic resonance spectroscopy (MRS) data and are not connected to detailed models for NVC. Therefore, we herein present a new model that integrates mechanistic modelling of both MRS and BOLD data. The metabolic model covers central metabolism, using a minimal set of interactions, and can describe time-series data for glucose, lactate, aspartate, and glutamate, measured after visual stimuli. Statistical tests confirm that the model can describe both estimation data and predict independent validation data, not used for model training. The interconnected NVC model can simultaneously describe BOLD data and can be used to predict expected metabolic responses in experiments where metabolism has not been measured. This model is a step towards a useful and mechanistically detailed model for cerebral blood flow and metabolism, with potential applications in both basic research and clinical applications.
Funder
Vetenskapsrådet
Centrum för Industriell Informationsteknologi, Linköpings Universitet
Stiftelsen för Strategisk Forskning
Science for Life Laboratory
PRECISE4Q
Stiftelsen Forska Utan Djurförsök
Hjärnfonden
Excellence Center at Linköping – Lund in Information Technology
VisualSweden
VINNOVA
Publisher
Public Library of Science (PLoS)
Subject
Computational Theory and Mathematics,Cellular and Molecular Neuroscience,Genetics,Molecular Biology,Ecology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics
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