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

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 raisi...

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Authors: Jobst, Beatrice M., Atasoy, Selen, Ponce-Alvarez, Adrián, Sanjuán, Ana, Roseman, Leor, Kaelen, Mendel, Carhart-Harris, Robin L., Kringelbach, Morten L., Deco, Gustavo
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/46982
Online Access:http://hdl.handle.net/10230/46982
http://dx.doi.org/10.1016/j.neuroimage.2021.117809
Access Level:Open access
Keyword:Brain state
LSD
Functional MRI
Whole-brain modelling
Perturbation
Resting state networks
id ES_beac58657e2a309d0c59f9ba177fba0e
oai_identifier_str oai:repositori.upf.edu:10230/46982
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Increased sensitivity to strong perturbations in a whole-brain model of LSD
title Increased sensitivity to strong perturbations in a whole-brain model of LSD
spellingShingle Increased sensitivity to strong perturbations in a whole-brain model of LSD
Jobst, Beatrice M.
Brain state
LSD
Functional MRI
Whole-brain modelling
Perturbation
Resting state networks
title_short Increased sensitivity to strong perturbations in a whole-brain model of LSD
title_full Increased sensitivity to strong perturbations in a whole-brain model of LSD
title_fullStr Increased sensitivity to strong perturbations in a whole-brain model of LSD
title_full_unstemmed Increased sensitivity to strong perturbations in a whole-brain model of LSD
title_sort Increased sensitivity to strong perturbations in a whole-brain model of LSD
dc.creator.none.fl_str_mv Jobst, Beatrice M.
Atasoy, Selen
Ponce-Alvarez, Adrián
Sanjuán, Ana
Roseman, Leor
Kaelen, Mendel
Carhart-Harris, Robin L.
Kringelbach, Morten L.
Deco, Gustavo
author Jobst, Beatrice M.
author_facet Jobst, Beatrice M.
Atasoy, Selen
Ponce-Alvarez, Adrián
Sanjuán, Ana
Roseman, Leor
Kaelen, Mendel
Carhart-Harris, Robin L.
Kringelbach, Morten L.
Deco, Gustavo
author_role author
author2 Atasoy, Selen
Ponce-Alvarez, Adrián
Sanjuán, Ana
Roseman, Leor
Kaelen, Mendel
Carhart-Harris, Robin L.
Kringelbach, Morten L.
Deco, Gustavo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Brain state
LSD
Functional MRI
Whole-brain modelling
Perturbation
Resting state networks
topic Brain state
LSD
Functional MRI
Whole-brain modelling
Perturbation
Resting state networks
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/46982
http://dx.doi.org/10.1016/j.neuroimage.2021.117809
url http://hdl.handle.net/10230/46982
http://dx.doi.org/10.1016/j.neuroimage.2021.117809
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv NeuroImage. 2021 Jan 29;230:117809
info:eu-repo/grantAgreement/EC/H2020/945539
info:eu-repo/grantAgreement/EC/FP7/615539
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Increased sensitivity to strong perturbations in a whole-brain model of LSDJobst, Beatrice M.Atasoy, SelenPonce-Alvarez, AdriánSanjuán, AnaRoseman, LeorKaelen, MendelCarhart-Harris, Robin L.Kringelbach, Morten L.Deco, GustavoBrain stateLSDFunctional MRIWhole-brain modellingPerturbationResting state networksLysergic 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.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.Elsevier202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/46982http://dx.doi.org/10.1016/j.neuroimage.2021.117809reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNeuroImage. 2021 Jan 29;230:117809info:eu-repo/grantAgreement/EC/H2020/945539info:eu-repo/grantAgreement/EC/FP7/615539© 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/http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/469822026-06-12T07:21:37Z
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