Causal analyses of relaxed beliefs under psychedelics (REBUS) in the default mode network

Abstract

The REBUS hypothesis aims to give a mechanistic explanation of the phenomenological effects experienced by humans under the influence of psychedelic drugs [1]. REBUS postulates that transmodal association networks (e.g., the default mode network [DMN]), which are thought to be the origin of high-level beliefs about possible interpretations of sensory inputs, exert a decreased influence on lower-level networks, whereas influence in the opposite direction increases. In these analyses, two lower-level regions have been identified as interesting candidates to test the causal claims derived from the REBUS hypothesis. First, the connectivity of the primary visual cortex (V1) with the DMN is intriguing as previous work [2] has shown that the V1 and the DMN are situated at opposite ends of the principal gradient of macroscale cortical organization. Second, recent results [3] indicate that psilocybin leads to a long-term decrease in functional connectivity between the hippocampus and the DMN. This suggests that the principles set out by REBUS could also underlie hippocampus-DMN connectivity. Our group has previously conducted placebo-controlled fMRI experiments with psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) [4,5,6]. We are interested in acute effective (i.e., directed) connectivity (EC) alterations between the mentioned lower-level regions and the DMN. [1] Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews, 71(3), 316-344. [2] Margulies, D. S. et al. (2016). Situating the default-mode network along a principal gradient of macroscale cortical organization. Proceedings of the National Academy of Sciences, 113(44), 12574-12579. [3] Siegel et al. (preprint): Psilocybin desynchronizes brain networks. https://doi.org/10.1101/2023.08.22.23294131 [4] Carhart-Harris, R. L. et al. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138-2143. [5] Carhart-Harris, R. L. et al. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences, 113(17), 4853-4858. [6] Timmermann, C. et al. (2023). Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences, 120(13), e2218949120.

Topics & conditions

Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.

Keywords