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

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  • Beatrice M. Jobst, Pompeu Fabra University
  • ,
  • Selen Atasoy, University of Oxford, Aarhus University
  • ,
  • Adrián Ponce-Alvarez, Pompeu Fabra University
  • ,
  • Ana Sanjuán, Pompeu Fabra University
  • ,
  • Leor Roseman, Imperial College London
  • ,
  • Mendel Kaelen, Imperial College London
  • ,
  • Robin Carhart-Harris, Imperial College London
  • ,
  • Morten L. Kringelbach
  • Gustavo Deco, Pompeu Fabra University, ICREA, Max Planck Institute for Human Cognitive and Brain Sciences, Monash University

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.

Original languageEnglish
Article number117809
Number of pages14
Publication statusPublished - Apr 2021

    Research areas

  • Brain state, Functional MRI, LSD, Perturbation, Resting state networks, Whole-brain modelling

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