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A Model-Driven Meta-Analysis Supports the Emerging Consensus View that Inhibitory Neurons Dominate BOLD-fMRI Responses
Department of Biomedical Engineering, Linköping University, Linköping, Sweden.
Department of Biomedical Engineering, Linköping University, Linköping, Sweden.
Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
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2024 (English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Functional magnetic resonance imaging (fMRI) is a pivotal tool for mapping neuronal activity in the brain. Traditionally, the observed hemodynamic changes are assumed to reflect the activity of the most common neuronal type: excitatory neurons. In contrast, recent experiments, using optogenetic techniques, suggest that the fMRI-signal instead reflects the activity of inhibitory interneurons. However, these data paint a complex picture, with numerous regulatory interactions, and where the different experiments display many qualitative differences. It is therefore not trivial how to quantify the relative contributions of the different cell types and to combine all observations into a unified theory. To address this, we present a new model-driven meta-analysis, which provides a unified and quantitative explanation for all data. This model-driven analysis allows for quantification of the relative contribution of different cell types: the contribution to the BOLD-signal from the excitatory cells is <20 % and 50-80 % comes from the interneurons. Our analysis also provides a mechanistic explanation for the observed experiment-to-experiment differences, e.g. a biphasic vascular response dependent on different stimulation intensities and an emerging secondary post-stimulation peak during longer stimulations. In summary, our study provides a new, emerging consensus-view supporting the larger role of interneurons in fMRI.

Place, publisher, year, edition, pages
2024. article id 2024.10.15.618416
Keywords [en]
BOLD, NVC, OIS, fMRI, inhibitory neurons, mathematical modelling
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:oru:diva-117153DOI: 10.1101/2024.10.15.618416PubMedID: 39464088OAI: oai:DiVA.org:oru-117153DiVA, id: diva2:1909775
Note

bioRxiv: 2024.10.15.618416

Available from: 2024-11-01 Created: 2024-11-01 Last updated: 2024-11-01Bibliographically approved

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Cedersund, Gunnar

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