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Model-driven meta-analysis establishes a new consensus view: 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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2025 (Engelska)Ingår i: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 197, nr Pt A, artikel-id 111014Artikel i tidskrift (Refereegranskat) Published
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 could reflect the activity of inhibitory interneurons. However, these data paint a complex picture, with numerous regulatory interactions, and with responses that sometimes seem to point in different directions. It is therefore not trivial how to quantify the relative contributions of the different cell types into a consensus view compatible with the considered data. To address this, we present a new model-driven meta-analysis, which provides a unified and quantitative explanation for the considered 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. For instance, one of the reasons that data seem to point in different directions is a biphasic vascular response, with a transient increase and a subsequent decrease. Our model-based data analysis explains why this biphasic response appears only for high-intensity stimulations and not for low-intensity stimulations. In other words, our meta-analysis goes beyond a simple vote-by-majority and provides a single unified explanation for the considered data. This explanation provides a consensus view that constitutes a paradigm shift in how fMRI can, and cannot, be used to interpret neuronal activity.

Ort, förlag, år, upplaga, sidor
Elsevier, 2025. Vol. 197, nr Pt A, artikel-id 111014
Nyckelord [en]
BOLD, Inhibitory neurons, Mathematical modelling, NVC, OIS, fMRI
Nationell ämneskategori
Biofysik
Identifikatorer
URN: urn:nbn:se:oru:diva-123639DOI: 10.1016/j.compbiomed.2025.111014PubMedID: 40926439Scopus ID: 2-s2.0-105015142418OAI: oai:DiVA.org:oru-123639DiVA, id: diva2:1997369
Forskningsfinansiär
Vetenskapsrådet, 2018–05418, 2018–03319Stiftelsen för strategisk forskning (SSF), ITM17-0245Knut och Alice Wallenbergs Stiftelse, 2020.0182EU, Horisont 2020Stiftelsen Forska utan djurförsök, F2019-0010Vinnova, 2020–04711EU, Horisont Europa, 101080875KK-stiftelsen, 20200017Vetenskapsrådet, 2022–02886NIH (National Institutes of Health), U24EB028998NIH (National Institutes of Health), NYS SCIRB DOH01-C38328GGNIH (National Institutes of Health), NIMH P50MH109429
Anmärkning

Funding Agencies:

GC acknowledges support from the Swedish Research Council (2018–05418, 2018–03319), CENIIT (15.09), the Swedish Foundation for Strategic Research (ITM17-0245), SciLifeLab National COVID-19 Research Program financed by the Knut and Alice Wallenberg Foundation (2020.0182), the H2020 project PRECISE4Q (777107), the Swedish Fund for Research without Animal Experiments (F2019-0010), ELLIIT (2020-A12), VINNOVA (VisualSweden, 2020–04711), and the Horizon Europe project STRATIF-AI (101080875). GC acknowledges scientific support from the Exploring Inflammation in Health and Disease (X-HiDE) Consortium, which is a strategic research profile at Örebro University funded by the Knowledge Foundation (20200017). ME acknowledges support from the Swedish Research Council (2022–02886). SDB acknowledges support from NIH U24EB028998, NYS SCIRB DOH01-C38328GG and NIMH P50MH109429.

Tillgänglig från: 2025-09-12 Skapad: 2025-09-12 Senast uppdaterad: 2026-01-23Bibliografiskt granskad

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