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Related Experiment Video

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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
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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.

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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.