Psilocybin induces dose-dependent changes in functional network organization in rat cortex
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson, Tiecheng Liu, Peter R. Guzzo, Jim Gilligan, UnCheol Lee, George A. Mashour, Giancarlo Vanini, Dinesh Pal
bioRxiv (Cold Spring Harbor Laboratory) February 12, 2024 preprint DOI: 10.1101/2024.02.09.579718 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study |
|---|---|
| Sample size | 12 |
| Population | Male and female rats |
| Intervention | Psilocybin |
| Dose | 0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour |
| Topics | Psilocybin |
| Keywords | High gamma oscillations Phase-amplitude coupling Rat Weighted phase-lag index Psychedelics psilocybin Hallucinogens Neural pathways Brain circuits Theta |
| Citations | 3 |
| Key findings | Psilocybin dose-dependently disrupted theta-gamma coupling, increased frontal high gamma and posterior theta connectivity and network density, and produced nonlinear changes in medium gamma frontoparietal connectivity. |
Abstract
Abstract Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex ( n =6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [ p <0.05], 2) increased frontal high gamma connectivity [ p <0.05] and posterior theta connectivity [ p ≤0.049], and 3) increased frontal high gamma [ p <0.05] and posterior theta [ p ≤0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 3
- Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression. Psychopharmacology July 4, 2024
- Restoring Oscillatory Dynamics in Alzheimer’s Disease: A Laminar Whole-Brain Model of Serotonergic Psychedelic Effects bioRxiv (Cold Spring Harbor Laboratory) December 16, 2024
- Psilocybin has a narrow therapeutic window as an antidepressant treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry April 2, 2025
Cites 29
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
and 24 more in the library