Increased sensitivity to strong perturbations in a whole-brain model of LSD.
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez, Ana Sanjuán, Leor Roseman, Mendel Kaelen, Robin Carhart-Harris, Morten L. Kringelbach, Gustavo Deco
Neuroimage January 29, 2021 DOI: 10.1016/j.neuroimage.2021.117809 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Computational modeling study with experimental fMRI data Peer reviewed |
|---|---|
| Population | Human participants under LSD or placebo |
| Intervention | LSD |
| Topics | LSD |
| Keywords | Brain models Perception Cognition |
| Citations | 37 |
| Key findings | LSD intake shifts the brain's global working point further from stable equilibrium and increases dynamical complexity and response diversity across brain regions, especially in limbic, visual, and default mode 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.
Comparable studies
Other experimental studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 25
- Default Mode Network Modulation by Psychedelics: A Systematic Review The International Journal of Neuropsychopharmacology October 21, 2022
- Canalization and plasticity in psychopathology Neuropharmacology December 27, 2022
- A complex systems perspective on psychedelic brain action. Trends in Cognitive Sciences February 3, 2023
- Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews November 30, 2023
- Pattern breaking: a complex systems approach to psychedelic medicine Neuroscience of Consciousness 2023
and 20 more in the library
Cites 38
- Breakdown of Cortical Effective Connectivity During Sleep Science September 29, 2005
- A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior Science Translational Medicine August 14, 2013
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 33 more in the library