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Intravenous psilocybin induces dose-dependent changes in functional network organization in rat cortex.
Brian H Silverstein1,2, Nicholas Kolbman1,2,3, Amanda Nelson1
1Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
Translational Psychiatry
|March 25, 2025
Summary
Psilocybin alters brain network dynamics in rats, disrupting theta-gamma coupling and increasing frontal high gamma and posterior theta connectivity in a dose-dependent manner. These changes in network organization may signify psilocybin-induced altered states of consciousness.
Area of Science:
- Neuroscience
- Psychopharmacology
- Computational Neuroscience
Background:
- Psilocybin induces altered states of consciousness with complex cortical network changes.
- Rodent models are crucial for studying psilocybin's mechanisms.
- Previous rodent studies lacked spatial resolution for network analysis and were limited to lower gamma frequencies.
Purpose of the Study:
- To characterize psilocybin's effects on cortex-wide network dynamics in rats using high-density electroencephalography (EEG).
- To investigate dose-dependent changes in brain network organization, including node degree and connection strength.
- To analyze alterations in theta-gamma phase-amplitude coupling.
Main Methods:
- EEG recordings from 27 cortical sites in rats (male and female).
- Administration of psilocybin at doses of 0.1, 1, and 10 mg/kg.
- Analysis of network properties (node degree, connection strength) in theta, medium gamma, and high gamma frequency bands after removing aperiodic EEG components.
- Assessment of theta-gamma phase-amplitude coupling.
Main Results:
- Psilocybin dose-dependently disrupted theta-gamma coupling.
- Increased frontal high gamma and posterior theta connectivity and network density were observed.
- Medium gamma frontoparietal connectivity and behavioral activity exhibited an inverted-U relationship with psilocybin dose.
Conclusions:
- Psilocybin significantly alters brain network organization in a dose-dependent manner.
- High-frequency network activity, independent of local theta phase, appears critical for psilocybin-induced altered states.
- This study provides a detailed network-level characterization of psilocybin's effects in a rodent model.
