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

Jobst, B. M., Atasoy, S., Ponce-Alvarez, A., Sanjuán, A., Roseman, L., Kaelen, M., et al. (2021). Increased sensitivity to strong perturbations in a whole-brain model of LSD. NeuroImage, 230: 117809. doi:10.1016/j.neuroimage.2021.117809.

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 Creators:
Jobst, Beatrice M.1, Author
Atasoy, Selen2, 3, Author
Ponce-Alvarez, Adrián1, Author
Sanjuán, Ana1, Author
Roseman, Leor4, Author
Kaelen, Mendel4, Author
Carhart-Harris, Robin4, Author
Kringelbach, Morten L.2, 3, Author
Deco, Gustavo1, 5, 6, 7, Author              
Affiliations:
1Computational Neuroscience Group, Department of Information and Communication Technologies, Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
2Department of Psychiatry, University of Oxford, United Kingdom, ou_persistent22              
3Center for Music in the Brain, Aarhus University, Denmark, ou_persistent22              
4Psychedelic Research Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom, ou_persistent22              
5Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
6Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634551              
7School of Psychological Sciences, Monash University, Melbourne, Australia, ou_persistent22              

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Free keywords: Brain state; LSD; Functional MRI; Whole-brain modelling; Perturbation; Resting state networks
 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.

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Language(s): eng - English
 Dates: 2021-01-022020-07-312021-01-252021-01-292021-04-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.neuroimage.2021.117809
Other: online ahead of print
PMID: 33524579
 Degree: -

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Project name : -
Grant ID : 945539
Funding program : Human Brain Project
Funding organization : -
Project name : -
Grant ID : 615539
Funding program : -
Funding organization : European Research Council
Project name : -
Grant ID : DNRF117
Funding program : -
Funding organization : Danish National Research Foundation

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Title: NeuroImage
Source Genre: Journal
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Publ. Info: Orlando, FL : Academic Press
Pages: - Volume / Issue: 230 Sequence Number: 117809 Start / End Page: - Identifier: ISSN: 1053-8119
CoNE: https://pure.mpg.de/cone/journals/resource/954922650166