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Psilocybin Desynchronizes Brain Networks

Joshua S. Siegel, Subha Subramanian, Nico U.f. Dosenbach, Ginger E. Nicol

Biological Psychiatry April 29, 2024 DOI: 10.1016/j.biopsych.2024.02.132 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Longitudinal precision functional mapping Peer reviewed
Population Healthy adults
Interventions Psilocybin Methylphenidate
Duration Up to 3 weeks post-dose, with follow-up at 6+ months
Topics Psilocybin
Keywords Hallucinogen Pharmacology
Citations 14
Key findings Psilocybin disrupts connectivity across cortical networks and subcortical structures, driven by desynchronization of brain activity, with persistent decrease in hippocampal-DMN connectivity lasting weeks but normalizing after six months.

Abstract

1 Summary The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding , connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin’s pro-plasticity and anti-depressant effects.

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