Collapse of directed functional hierarchy under classical serotonergic psychedelics
Poster No:
41
Submission Type:
Abstract Submission
Authors:
Jakub Vohryzek1, Morten Kringelbach2, Edmundo Lopez-Sola3, Elvira Garcia-Guzman4, Christopher Timmermann5, Leor Roseman6, Enzo Tagliazucchi7, Giulio Ruffini3, Robin Carhart-Harris8, Gustavo Deco4, Yonatan Sanz-Perl9
Institutions:
1UNIVERSITAT POMPEU FABRA, Barcelona, catalunya, 2University of Oxford, Oxford, Oxfordshire, 3Neuroelectrics, Barcelona, Catalunya, 4University Pompeu Fabra, Barcelona, Catalunya, 5University College London, London, London, 6University of Exeter, Exeter, Devon, 7Universidad Adolfo Ibáñez, Santiago, RM, 8University of California San Francisco, San Francisco, CA, 9Universitat Pompeu Fabra, Barcelona, Barcelona
First Author:
Co-Author(s):
Introduction:
Classical serotonergic psychedelics desynchronise brain dynamics (Siegel et al., 2024), inducing profound functional changes to the hierarchical organization of the human brain (Girn et al., 2022). Yet the term hierarchy is loosely defined in neuroscience. Here, we used a concrete definition of hierarchy, grounded in the theory of thermodynamics, which quantifies the temporal asymmetry in the directionality of information flow (Deco et al., 2024; Kringelbach et al., 2024). We investigated the changes to the brain functional organization under three classical serotonergic psychedelics – psilocybin, LSD and DMT (Carhart-Harris et al., 2012; Carhart-Harris et al., 2016; Timmermann et al., 2023). We found that the acute effects of psychedelics induce a collapse of the directed functional hierarchy at the global and network level compared to the participants in the control conditions. Crucially, our results provide evidence that brain's directed functional hierarchy is collapsed under psychedelics, and thus yields a democratization of brain organization compatible with more flexibility (Carhart-Harris & Friston, 2019).
Methods:
Neuroimaging fMRI data of whole-brain dynamics before and during the intervention with psychedelic compounds – psilocybin (n=9), LSD (n=15) and DMT (n=17) (Carhart-Harris et al., 2012; Carhart-Harris et al., 2016; Timmermann et al., 2023) were used for this study (Figure 1A). The pairwise temporal asymmetry was measured as a time-shifted correlation between brain regions of interest x and y with a time shift of one TR (Figure 1B). At the whole-brain level temporal asymmetry was summarized in an asymmetric matrix represented by the time shifted correlation matrix. The magnitude of temporal asymmetry was defined as the square of the difference between time-shifted correlations of regions x and y, and time-shifted correlations of regions y and x (Figure 1C). The main hypothesis was that directed functional hierarchy under psychedelics decreases compared to the pre-intervention state and control condition (Figure 1D).
·Figure 1. Calculation of brain directed functional hierarchy under psychedelics.
Results:
We found that after administration of psychedelics the directed functional hierarchy is significantly decreased compared to the placebo condition (PCB) pre and post administration, and compared with the before administration of psychedelics (two-tailed paired t-test, DMT dataset: DMT post vs. DMT pre, p<10-4, DMT post vs. PCB post, p<10-4, PCB post vs. PCB pre, p=0.419., LSD dataset: LSD post vs. LSD pre, p=3x10-4, PSILOCYBIN dataset: PSILO post vs. PSILO pre, p=0.022, PSILO post vs. PCB post, p=0.057, PCB post vs. PCB pre, p=0.79) (Figure 2A). We investigated how the magnitude of temporal asymmetry of each resting-state network (RSN) becomes altered under psychedelics compared to the PCB condition and before the doses administration. We found that Default Mode Network (DMN), Fronto-Parietal Network (FPA) and Dorsal Attention Network (DAN) consistently decrease the directed functional hierarchy during psychedelic states (black asterix denotes statistics of fdr corrected two-tailed paired t-test with p-values < 0.05) (Figure 2B). Lastly, we looked at how the directed functional hierarchy interactions between RSN are modified under psychedelics. In Figure 2C, we report the interaction matrices for each dataset and for each condition averaged across participants assessing the statistical differences between conditions in term of paired t-test false discovery rate corrected (white entries) and without correction (grey entries).
·Figure 2. Directed functional hierarchy at the global and network under psychedelics.
Conclusions:
Overall, our findings suggest that the acute effects of psychedelics lead to a collapse of the directed functional hierarchy at the global and network level compared to controls in the resting-state condition. Motivated by principles of thermodynamics, the present work broadens our understanding of functional hierarchy and its alterations under psychedelics.
Brain Stimulation:
Non-Invasive Stimulation Methods Other 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling 2
Keywords:
Computational Neuroscience
FUNCTIONAL MRI
Other - Asymmetric connectivity; Temporal Hierarchy; Psychedelics; Latent Space; Thermodynamics
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
Carhart-Harris, R. L. (2019). REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacological Reviews, 71(3), 316-344. https://doi.org/10.1124/pr.118.017160
Carhart-Harris, R. L. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of National Academy of Sciences U S A, 113(17), 4853-4858. https://doi.org/10.1073/pnas.1518377113
Deco, G. (2024). Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression. Nature Mental Health, 2(9), 1096-1110.
Girn, M. (2022). Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex. Neuroimage, 256, 119220.
Kringelbach, M. L. (2024). The Thermodynamics of Mind. Trends in cognitive sciences.
Siegel, J. S. (2024). Psilocybin desynchronizes the human brain. Nature, 632(8023), 131-138.
Timmermann, C. (2023). Human brain effects of DMT assessed via EEG-fMRI. Proceedings of National Academy of Sciences U S A, 120(13), e2218949120. https://doi.org/10.1073/pnas.2218949120