Increased sensitivity to strong perturbations in a whole-brain model of LSD

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• dc.contributor.author Jobst, Beatrice M.
• dc.contributor.author Atasoy, Selen
• dc.contributor.author Ponce-Alvarez, Adrián
• dc.contributor.author Sanjuán, Ana
• dc.contributor.author Roseman, Leor
• dc.contributor.author Kaelen, Mendel
• dc.contributor.author Carhart-Harris, Robin L.
• dc.contributor.author Kringelbach, Morten L.
• dc.contributor.author Deco, Gustavo
• dc.date.accessioned 2021-03-30T07:57:37Z
• dc.date.available 2021-03-30T07:57:37Z
• dc.date.issued 2021
• dc.description.abstract Lysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain's global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.
• dc.description.sponsorship BMJ, AP-A, AS and GD are supported by AWAKENING Using wholebrain models perturbational approaches for predicting external stimulation to force transitions between different brain states (ref. PID2019-105772GB-I00 /AEI/10.13039/501100011033), funded by the Spanish Ministry of Science Innovation and Universities (MCIU) and State Research Agency (AEI), the HBP SGA3 Human Brain Project Specific Grant Agreement 3 (Grant Agreement No. 945539), funded by the EU H2020 FET Flagship program, the SGR Research Support Group support (ref.2017 SGR 1545), funded by the Catalan Agency for Management of University and Research Grants (AGAUR), the SEMAINE ERA-Net NEURON Project, a Juan de la Cierva fellowship (IJCI-2014–21066) from the Spanish Ministry of Economy and Competitiveness, a Juan de la Cierva fellowship from the Spanish Ministry of Economy and Competitiveness (FPDI2013–17045), and by the FLAG-ERA JTC (PCI2018–092891). RC-H is supported by the Alex Mosley Charitable Trust, Ad Astra Chandaria Foundation, Nikean Foundation, Tim Ferriss, Alexander and Bohdana Tamas and Anton Bilton. SA and MLK are supported by the ERC Consolidator Grant: CAREGIVING (n. 615539), Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117), and centre for Eudaimonia and Human Flourishing funded by the Pettit and Carlsberg Foundations.
• dc.format.mimetype application/pdf
• dc.identifier.citation Jobst BM, Atasoy S, Ponce-Alvarez A, Sanjuán A, Roseman L, Kaelen, Carhart-Harris R, Kringelbach ML, Deco G. Increased sensitivity to strong perturbations in a whole-brain model of LSD. Neuroimage. 2021 Jan 29;230:117809. DOI: 10.1016/j.neuroimage.2021.117809
• dc.identifier.doi http://dx.doi.org/10.1016/j.neuroimage.2021.117809
• dc.identifier.issn 1053-8119
• dc.identifier.uri http://hdl.handle.net/10230/46982
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof NeuroImage. 2021 Jan 29;230:117809
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/945539
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/615539
• dc.rights © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license 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.keyword Brain state
• dc.subject.keyword LSD
• dc.subject.keyword Functional MRI
• dc.subject.keyword Whole-brain modelling
• dc.subject.keyword Perturbation
• dc.subject.keyword Resting state networks
• dc.title Increased sensitivity to strong perturbations in a whole-brain model of LSD
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion