Psilocybin desynchronizes brain networks
Using dense longitudinal fMRI mapping, a single high dose of psilocybin massively desynchronised cortical and subcortical functional connectivity—dissolving within-network correlations and between-network anticorrelations—far more than methylphenidate and with the strongest effect in the default mode network. These acute changes tracked subjective experience, were attenuated by a perceptual task, and included a persistent reduction in anterior hippocampus–DMN coupling lasting weeks that may underlie psilocybin’s proplasticity and therapeutic effects.
Abstract
A single dose of psilocybin, a psychedelic that acutely causes distortions of space–time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials 1–4 . In animal models, psilocybin induces neuroplasticity in cortex and hippocampus 5–8 . It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6–12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.
Research Summary of 'Psilocybin desynchronizes brain networks'
Introduction
Earlier research shows that a single high dose of psilocybin produces rapid, sometimes long-lasting therapeutic effects in humans and induces synaptogenesis and other plasticity-related changes in animal models. However, how macroscopic human brain networks change acutely and persistently after psychedelic exposure, and how those changes relate to subjective experiences such as ego dissolution or altered time/space perception, remains unclear. Previous human studies reported reduced network segregation, increased metabolic activity and altered electrophysiological power during the acute psychedelic state, but lacked the longitudinal, individual-specific resolution needed to link network dynamics to subjective effects and to persistent neuroplastic changes. This study set out to map individual-specific brain network changes before, during and after high-dose oral psilocybin using intensive longitudinal precision functional mapping. Siegel and colleagues compared psilocybin (25 mg) with an active stimulant control (40 mg methylphenidate, MTP), related functional connectivity (FC) changes to subjective psychedelic intensity (MEQ30), tested whether task engagement modulates those changes, quantified a measure of spatial desynchronization (NGSC) and examined whether any FC changes persist for up to three weeks and at a 6–12 month replication visit. The study therefore aimed to connect acute network-level effects, subjective experience and candidate persistent circuit-level changes that could plausibly underlie pro-plasticity and therapeutic mechanisms.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Siegel, J. S., Subramanian, S., Perry, D., Kay, B. P., Gordon, E. M., Laumann, T. O., Reneau, T. R., Metcalf, N. V., Chacko, R. V., Gratton, C., Horan, C., Krimmel, S. R., Shimony, J. S., Schweiger, J. A., Wong, D. F., Bender, D. A., Scheidter, K. M., Whiting, F. I., Padawer-Curry, J. A., . . . Dosenbach, N. U. F. (2024). Psilocybin desynchronizes brain networks. Nature, 632(8023), 131-138. https://doi.org/10.1038/s41586-024-07624-5
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