Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness

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• dc.contributor.author Mindlin, Ivan
• dc.contributor.author Herzog, Rubén
• dc.contributor.author Belloli, Laouen
• dc.contributor.author Manasova, Dragana
• dc.contributor.author Monge-Asensio, Martí
• dc.contributor.author Vohzyzek, Jakub
• dc.contributor.author Escrichs, Anira
• dc.contributor.author Alnagger, Naji
• dc.contributor.author Núñez, Paul L.
• dc.contributor.author Gosseries, Olivia
• dc.contributor.author kringelbach, Morten L.
• dc.contributor.author Deco, Gustavo
• dc.contributor.author Tagliazucchi, Enzo Rodolfo
• dc.contributor.author Naccache, Lionel
• dc.contributor.author Rohaut, Benjamin
• dc.contributor.author Sitt, Jacobo Diego
• dc.contributor.author Sanz Perl, Yonatan
• dc.date.accessioned 2025-05-21T05:57:25Z
• dc.date.available 2025-05-21T05:57:25Z
• dc.date.issued 2024
• dc.description.abstract Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigations and the mechanisms behind them are methodologically and ethically constrained. To tackle these limitations, we combined biologically plausible whole-brain models with deep learning techniques to characterise the low-dimensional space of DoC patients. We investigated the effects of model pharmacological interventions by including the whole-brain dynamical consequences of the enhanced neuromodulatory level of different neurotransmitters, and providing geometrical interpretation in the low-dimensional space. Our findings show that serotonergic and opioid receptors effectively shifted the DoC models towards a dynamical behaviour associated with a healthier state, and that these improvements correlated with the mean density of the activated receptors throughout the brain. These findings mark an important step towards the development of treatments not only for DoC but also for a broader spectrum of brain diseases. Our method offers a promising avenue for exploring the therapeutic potential of pharmacological interventions within the ethical and methodological confines of clinical research.
• dc.description.sponsorship The authors express gratitude to all the individuals who participated in the studies. Additionally, we extend our thanks to the dedication and support provided by the clinicians at the Neuro ICU, DMU Neurosciences, APHP Sorbonne Université, Hôpital de la Pitié Salpêtrière, Paris, France. Moreover, we acknowledge the invaluable contributions of patient families whose consent and understanding significantly contribute to the advancement of the field. We finally thank the financial support of the FLAG-ERA research funding organisation (project ModelDXConsciousness). Y.S.P.is supported by European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant 896354, and ‘ERDF A way of making Europe’, ERDF, EU, Project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe. M.L.K. is supported by the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117), and Centre for Eudaimonia and Human Flourishing at Linacre College funded by the Pettit and Carlsberg Foundations. ET is supported by grants FONCYT-PICT (2019-02294), CONICET-PIP (11220210100800CO), and ANID/FONDECYT Regular (1220995). O.G. is research associate and N.A. is research fellow at FNRS. G.D. is supported by grant no. PID2022-136216NB-I00 funded by MICIU/AEI/10.13039/501100011033 and by ‘ERDF A way of making Europe’, ERDF, EU, Project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe, and AGAUR research support grant (ref. 2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Mindlin I, Herzog R, Belloli L, Manasova D, Monge-Asensio M, Vohzyzek J, et al. Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness. Commun Biol. 2024;7:1176. DOI: 10.1038/s42003-024-06852-9
• dc.identifier.doi http://dx.doi.org/10.1038/s42003-024-06852-9
• dc.identifier.issn 2399-3642
• dc.identifier.uri http://hdl.handle.net/10230/70444
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Communications Biology. 2024;7:1176
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/896354
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101071900
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136216NB-I00
• dc.rights © The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Consciència
• dc.subject.other Cervell -- Models
• dc.subject.other Farmacologia
• dc.title Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion