Unmixing the Psychedelic Connectome: Brain Network Traits of Psilocybin
Krishna Prasad Bhavaraju, Natasha L. Mason, Pablo Mallaroni, Dietmar Heinke, Stefan W. Toennes, Johannes G. Ramaekers, Enrico Amico
November 17, 2025 preprint DOI: 10.1101/2025.11.17.688834 via OpenAlex
Summary
AI-generated from the abstractPsilocybin alters consciousness through multiple distinct neural processes rather than a single, uniform change in brain connectivity. Using a data-driven method called Connectome Independent Component Analysis on resting-state fMRI data from healthy volunteers, researchers identified separate functional connectivity traits. One trait was linked to the drug's physiological action, as its expression varied with plasma psilocin levels. A second, independent trait was associated with worse performance on a visual divergent thinking task. These results show the acute psilocybin state comprises co-occurring neural patterns, validating a decompositional approach to disentangle pharmacological and cognitive effects.
Study at a glance
| Characteristics | Observational study |
|---|---|
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Trait Cognition Neuroimaging Functional connectivity |
| Key finding | The acute psilocybin state is a composite of co-occurring neural processes, with one functional connectivity trait linked to plasma psilocin concentration and another independently associated with impaired visual divergent thinking performance. |
Abstract
Abstract Psilocybin induces profound alterations in consciousness, yet prevailing neural models often describe a monolithic change in brain connectivity that may not fully capture the multifaceted nature of the psychedelic state. To test the hypothesis of a composite neural state, this study applied a robust, data-driven framework, Connectome Independent Component Analysis (connICA) with multi-level resampling, to resting-state fMRI data from healthy volunteers. The analysis decomposed connectomes into statistically independent functional connectivity traits ("FC-Traits"), revealing a primary trait whose expression was significantly modulated by plasma psilocin concentration, providing a whole-cortical signature of the drug’s physiological action. Crucially, a second, distinct trait was also isolated, which independently associated with impaired performance on a visual divergent thinking task. These findings demonstrate that the acute psilocybin state is a composite of co-occurring neural processes. This validates the application of a decompositional connectomic framework to move beyond global descriptions and successfully disentangle the specific neural patterns underlying distinct pharmacological and cognitive correlates.