Psilocybin induces dose-dependent changes in functional network organization in rat cortex
OpenAlex – February 12, 2024
Source: OpenAlex
Summary
Psilocybin, a potent hallucinogen, profoundly alters brain functional organization. Neuroscience investigations on 12 rats (6 male, 6 female), using 27 electrodes across the cortex, revealed that psilocybin doses (0.1-10 mg/kg) disrupted how theta and gamma brain waves synchronize. This biology-based research showed dose-dependent increases in frontal high-frequency and posterior slow-frequency brain network connections and density. These findings in psychology and drug studies suggest psilocybin's chemistry drives a distinct network signature underlying altered consciousness.
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.