Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.
Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neur...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4911100?pdf=render |
| _version_ | 1828748794527744000 |
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| author | Karin Lundengård Gunnar Cedersund Sebastian Sten Felix Leong Alexander Smedberg Fredrik Elinder Maria Engström |
| author_facet | Karin Lundengård Gunnar Cedersund Sebastian Sten Felix Leong Alexander Smedberg Fredrik Elinder Maria Engström |
| author_sort | Karin Lundengård |
| collection | DOAJ |
| description | Functional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data. These results open the door to a new type of fMRI analysis that more accurately reflects the true neuronal activity. |
| first_indexed | 2024-04-14T06:47:40Z |
| format | Article |
| id | doaj.art-69be3d898ceb4cebba99b777377eb714 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-14T06:47:40Z |
| publishDate | 2016-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-69be3d898ceb4cebba99b777377eb7142022-12-22T02:07:08ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-06-01126e100497110.1371/journal.pcbi.1004971Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.Karin LundengårdGunnar CedersundSebastian StenFelix LeongAlexander SmedbergFredrik ElinderMaria EngströmFunctional magnetic resonance imaging (fMRI) measures brain activity by detecting the blood-oxygen-level dependent (BOLD) response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new, independent validation data. These results open the door to a new type of fMRI analysis that more accurately reflects the true neuronal activity.http://europepmc.org/articles/PMC4911100?pdf=render |
| spellingShingle | Karin Lundengård Gunnar Cedersund Sebastian Sten Felix Leong Alexander Smedberg Fredrik Elinder Maria Engström Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. PLoS Computational Biology |
| title | Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. |
| title_full | Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. |
| title_fullStr | Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. |
| title_full_unstemmed | Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. |
| title_short | Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI. |
| title_sort | mechanistic mathematical modeling tests hypotheses of the neurovascular coupling in fmri |
| url | http://europepmc.org/articles/PMC4911100?pdf=render |
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