A groundbreaking study published June 14 in Translational Psychiatry provides the most detailed map yet of how psilocybin—the psychoactive compound found in “magic mushrooms”—reshapes brain network dynamics in animal models. Using high-density electroencephalography (EEG) in rats, an international team led by the University of Michigan’s Lunar Labs Initiative (LLI) demonstrated that psilocybin disrupts normal patterns of neural communication, generating distinct phases of altered activity across theta and gamma frequency bands. These findings not only bolster the use of rodent models for probing the neurophysiology of psychedelic states but also lay a quantitative foundation for future therapeutic research.
Background: The Quest to Model Psychedelic States
Psilocybin has garnered intense scientific interest for its potential to treat treatment-resistant depression, anxiety, addiction, and other psychiatric conditions. In humans, functional MRI and EEG studies have revealed that psilocybin temporarily increases global brain connectivity and reduces the segregation of specialized networks—effects thought to underlie its perceptual and emotional alterations. However, human studies are limited by cost, subject variability, and the impossibility of invasive measurements. Rodent models offer the promise of controlled, mechanistic investigations but have struggled to establish objective biomarkers that correlate with the subjective experiences central to the psychedelic state.
“Any EEG-based evidence for a ‘psychedelic’ state in animal models brings us closer to understanding consciousness as a universal phenomenon,” said study author Dr. Dinesh Pal, associate professor at the University of Michigan.
Methods: High-Resolution EEG in Rats
To overcome past limitations, the researchers implanted 27-channel EEG electrode arrays across the neocortex of 12 adult Sprague Dawley rats (six male, six female). Over multiple sessions, each rat received 60-minute intravenous infusions of psilocybin at three dose levels—0.1, 1, and 10 mg/kg—as well as saline controls. Continuous EEG recordings captured the drug’s evolving effects, while synchronized video and motion-tracking sensors logged behavioral changes, including the characteristic head-twitch response (HTR) indicative of 5-HT2A receptor activation.
“By using a slow, steady infusion instead of a bolus injection, we could track gradual shifts in brain network organization,” explained Dr. Krystal Ruiz-Rocha, co–first author of the paper.
Analytical Focus: Theta, Medium Gamma, and High Gamma Bands
The investigators concentrated on three frequency bands known to coordinate neural communication:
- Theta (4–10 Hz): Associated with memory, attention, and large-scale network coordination.
- Medium Gamma (70–110 Hz): Linked to local processing and cognitive functions.
- High Gamma (110–150 Hz): Thought to reflect fine-scale cortical activity and potentially neuroplasticity.
They assessed each band’s power, interregional coherence, and phase–amplitude coupling (PAC)—the nesting of high-frequency oscillations within slower rhythms, a mechanism critical for information flow.
Results: Two Distinct Phases of Network Reorganization
Psilocybin’s effects unfolded nonlinearly, with dose- and time-dependent divergences between moderate (1 mg/kg) and high (10 mg/kg) infusion conditions.
Phase 1: Moderate Dose Enhances Posterior Theta and Frontal-Parietal Gamma
- Increased Posterior Theta Power: At 1 mg/kg, theta band activity strengthened in posterior cortical regions, suggesting heightened large-scale integration early in the infusion.
- Enhanced Frontal-Parietal Gamma Coherence: Both medium and high gamma bands exhibited greater long-range synchronization between frontal and parietal cortices, reflecting a breakdown of normal network modularity.
- Disrupted Phase–Amplitude Coupling: PAC between theta phase and gamma amplitude diminished significantly in frontal regions, indicating a decoupling of local processing from global timing cues.
Behaviorally, moderate doses induced a surge in head-twitch responses—peaking around 20 minutes—and a transient increase in locomotion, consistent with rodent models of psychedelic activation.
“The paradoxical coexistence of increased cortical connectivity with PAC disruption may underpin the flexible cognition seen under psychedelics,” noted co-author Dr. Anjali Yolkier.
Phase 2: High Dose Shifts to Frontal-Dominant Gamma as Posterior Theta Declines
- Initial Gamma Connectivity Spike: Early in the 10 mg/kg infusion, gamma coherence surged similarly to the moderate dose.
- Progressive Posterior Theta Suppression: As psilocybin accumulated, theta power in posterior areas fell below baseline, marking a departure from Phase 1 dynamics.
- Frontal Gamma Network Dominance: High gamma synchronization in frontal cortex became increasingly pronounced, even as overall motion and HTR rates declined after 30 minutes.
This divergence between brain network states and overt behavior suggests that the neural signatures of the psychedelic state persist independently of observable activation.
“Gamma connectivity remained elevated long after head twitches subsided, underscoring that these EEG changes do not merely track locomotion,” Pal emphasized.
Network Metrics: Node Degree and Synchronization Strength
Using graph-theoretical measures, the team quantified each region’s node degree (number of significant connections) and synchronization strength. Moderate doses increased node degree in posterior theta networks, while high gamma networks saw augmented node degrees in frontal regions across both dose levels. These metrics illustrate a profound reorganization of mesoscale brain architecture.
Phase–Amplitude Decoupling: A Hallmark of Psychedelic States
Under baseline conditions, gamma bursts reliably align to specific phases of the theta cycle—a coupling thought to gate information flow. Psilocybin disrupted this alignment in a dose-dependent manner, particularly at high doses, mirroring findings from human EEG studies of LSD and other serotonergic psychedelics. Such decoupling likely facilitates atypical neural information pathways, potentially underlying altered perception and cognition.
Implications for Consciousness Research and Therapeutics
These results provide the first robust EEG biomarkers of a “psychedelic-like” state in animal models, opening avenues for:
- Mechanistic Studies: Investigating how serotonin receptor subtypes mediate network reorganization, using pharmacological antagonists or genetic knockouts.
- Comparative Psychedelic Signatures: Mining existing datasets on ketamine, nitrous oxide, and DMT to identify shared EEG patterns across diverse non-ordinary states.
- Translational Applications: Correlating rodent EEG phenotypes with human clinical outcomes to refine dosing protocols and predict therapeutic response.
“If we can link specific network signatures to therapeutic efficacy, we could tailor psychedelic treatments for conditions like chronic pain and depression,” said Ruiz-Rocha, referencing ongoing rodent studies (PMID: 38113836).
Limitations and Future Directions
Key caveats temper the interpretation:
- Lack of Subjective Correlates: Without verbal reports, direct mapping of EEG changes to human-like psychedelic experiences remains speculative.
- Receptor Specificity: The study did not selectively block 5-HT2A or other receptors to determine causal pathways.
- Deep-Structure Blind Spots: Scalp EEG cannot capture activity in subcortical nuclei (e.g., thalamus, claustrum) hypothesized to play roles in psychedelic phenomenology.
Future work will address these gaps by combining EEG with intracranial recordings, receptor-targeted pharmacology, and possibly functional imaging, to build a comprehensive picture of how psilocybin alters consciousness from molecules to networks.
Broader Context: Towards a Lunar Gravitational-Wave Observatory
While tangential to the psychedelic focus, the LLI’s broader vision includes deploying advanced measurement platforms—such as lunar gravitational-wave detectors—to push scientific frontiers. Pal envisions training a new generation of interdisciplinary researchers capable of bridging neuroscience, physics, and space exploration.
“Just as we’re extending our gravitational-wave observatories from Earth to space and even the Moon, we must extend our neurophysiological tools to probe the deepest mysteries of the mind,” he concluded.
Conclusion
The LLI’s study marks a significant leap forward in modeling psychedelic brain states. By charting two distinct phases of psilocybin-induced network reorganization in rats, the researchers have identified measurable EEG signatures that resonate with human findings—most notably increased gamma coherence and theta–gamma decoupling. These insights lay the groundwork for rigorous mechanistic and therapeutic investigations, bringing us closer to decoding how altered neural connectivity gives rise to extraordinary shifts in perception, emotion, and cognition. As the field moves toward multimodal, translational research, rodent models armed with high-density EEG promise to illuminate the universal principles of consciousness—whether on Earth or beyond.
