Nonequilibrium brain dynamics elicited as the origin of perturbative complexity

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• dc.contributor.author Stikvoort, Wiep
• dc.contributor.author Pérez-Ordoyo, Eider
• dc.contributor.author Mindlin, Ivan
• dc.contributor.author Escrichs, Anira
• dc.contributor.author Sitt, Jacobo D.
• dc.contributor.author Kringelbach, Morten L.
• dc.contributor.author Deco, Gustavo
• dc.contributor.author Sanz Perl, Yonatan
• dc.date.accessioned 2025-11-10T06:40:35Z
• dc.date.available 2025-11-10T06:40:35Z
• dc.date.issued 2025
• dc.description.abstract Assessing someone’s level of consciousness is a complex matter, and attempts have been made to aid clinicians in these assessments through metrics based on neuroimaging data. Many studies have empirically investigated measures related to the complexity elicited after the brain is stimulated to quantify the level of consciousness across different states. Here we hypothesized that the level of non-equilibrium dynamics of the unperturbed brain already contains the information needed to know how the system will react to an external stimulus. We created personalized wholebrain models fitted to resting state fMRI data recorded in participants in altered states of consciousness (e.g., deep sleep, disorders of consciousness) to infer the effective connections underlying their brain dynamics. We then measured the outof-equilibrium nature of the unperturbed brain by evaluating the level of asymmetry of the inferred connectivity, the time irreversibility in each model and compared this with the elicited complexity generated after in silico perturbations, using a simulated fMRI-based version of the Perturbational Complexity Index, a measure that has been shown to distinguish different levels of consciousness in in vivo settings. Crucially, we found that states of consciousness involving lower arousal and/or lower awareness had a lower level of asymmetry in their effective connectivities, a lower level of irreversibility in their simulated dynamics, and a lower complexity compared to control subjects. We show that the asymmetry in the underlying connections drives the nonequilibrium state of the system and in turn the differences in complexity as a response to the external stimuli.en
• dc.description.sponsorship W.S. is an FI fellow with the support of AGAUR, Generalitat de Catalunya and Fondo Social Europeo (2022 FI_B 00152, https://agaur.gencat.cat/ca/inici). E.P. is an FPI fellow funded by the Spanish "Ministerio de Ciencia, Innovación y Universidades" (MICIU/AEI/10.13039/501100011033) and "ESF investing in your future" under the grant PRE2020-0961 (https://www.ciencia.gob.es/, https://european-social-fund-plus. ec.europa.eu/en). I.M. is funded by FLAGERA research funding organisation (project ModelDXConsciousness, https://www.flagera. eu/). G.D. and A.E. were supported by the Grant PID2022-136216NB-I00 funded by MICIU/AEI/10.13039/501100011033 and by “ERDF A way of making Europe,” ERDF, EU (https://ec.europa.eu/regional_policy/funding/erdf_en). G.D. and Y.S.P. were supported by the project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS) (ref. 101071900) funded by the EU ERC Synergy Horizon Europe (https://erc.europa.eu/applygrant/synergy-grant). A.E. was also supported by the project eBRAIN-Health - Actionable Multilevel Health Data (id 101058516), funded by the EU Horizon Europe (https://cordis.europa.eu/project/id/101058516). G.D. is also supported by AGAUR research support grant (2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya (https://agaur.gencat.cat/ca/inici). M.L.K. is supported by the Centre for Eudaimonia and Human Flourishing (funded by the Pettit and Carlsberg Foundations) and Center for Music in the Brain (funded by the Danish National Research Foundation, DNRF117, https://www.carlsbergfondet.dk/en/what-we-have-funded/cf20-0698/, https://dg.dk/en/). J.D.S. is supported by the EU ERA PerMed Joint Translational 2019 project (project PerBrain) and by the JTC-HBP project MODELDxConsciousness (https://erapermed.isciii.es/joint-transnational-call2019/, https://www.humanbrainproject.eu/en/collaborate-hbp/partnering-projects/modeldxconsciousness/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Stikvoort W, Pérez-Ordoyo E, Mindlin I, Escrichs A, Sitt JD, Kringelbach ML, et al. Nonequilibrium brain dynamics elicited as the origin of perturbative complexity. PLoS Comput Biol. 2025 Jun 6;21(6):e1013150. DOI: 10.1371/journal.pcbi.1013150
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1013150
• dc.identifier.issn 1553-734X
• dc.identifier.uri http://hdl.handle.net/10230/71815
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Computational Biology. 2025 Jun 6;21(6):e1013150
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101071900
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101058516
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136216NB-I00
• dc.rights © 2025 Stikvoort et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Termodinàmica del desequilibrica
• dc.subject.other Cervellca
• dc.subject.other Neurologiaca
• dc.title Nonequilibrium brain dynamics elicited as the origin of perturbative complexityen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion