A Seven-Layer Brain Architecture Framework Reveals Distinct Thalamic Dynamical Regimes Across Five Pharmacological Classes
Ryan Malone
Zenodo (CERN European Organization for Nuclear Research) April 27, 2026 preprint DOI: 10.5281/zenodo.19816438 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational neuroimaging study (resting-state fMRI analysis across drug classes) |
|---|---|
| Sample size | 73 |
| Population | People who received LSD, psilocybin, DMT, ketamine, or propofol and underwent resting-state fMRI |
| Interventions | LSD Psilocybin DMT Ketamine Propofol |
| Measures | Granger causality, dynamic functional connectivity variance (DV), cascade fraction metrics |
| Key findings | The authors report that each of five drug classes produces a distinct thalamic dynamical signature: LSD is said to freeze the thalamic filter while preserving arousal, psilocybin stabilizes dynamic connectivity (dz=−1.02), DMT produces transient hemispheric asymmetry, ketamine shows null thalamic effects (all p>0.30), and propofol shows autocorrelation collapse consistent with burst suppression. They argue that pharmacokinetic rate and receptor specificity determine the thalamic dynamical regime, supporting a filter-based account of drug-induced altered consciousness. |
Abstract
Understanding how psychoactive substances alter brain dynamics requires a framework that goesbeyond regional activation to characterise the hierarchical organisation of information flow. Weapply a seven-layer functional brain architecture — L1 Brainstem (Gain), L2 Claustrum/Insula(Antenna), L3 Basal Ganglia/TRN (Gate), L4 Thalamus (Filter), L5 Posterior Hubs (Workspace),L6 Hippocampus (Memory), L7 mPFC/ACC/Insula (Self) — to resting-state fMRI data from fivepharmacological classes: LSD (n=20), psilocybin (n=7, precision mapping), DMT (n=12),ketamine (n=30), and propofol (n=4, preliminary). Using Granger causality, dynamic functionalconnectivity variance (DV), and cascade fraction metrics, we demonstrate that each drug producesa distinct thalamic dynamical signature. LSD uniquely freezes the thalamic filter (lowest cascadestrength=91.1, lowest dynamic variance=0.088, most stable layer=Thalamus [DV=0.077]) whilepreserving arousal. Psilocybin stabilises dynamic connectivity (dz=−1.02, p=0.036). DMTproduces transient hemispheric asymmetry (p=0.028). Ketamine produces null thalamic effects(all p>0.30), confirming the NMDA pathway does not converge on the TRN-thalamic circuit.Propofol produces autocorrelation collapse consistent with burst suppression. These resultsestablish pharmacokinetic rate and receptor specificity as determinants of thalamic dynamicalregime and support a filter-based account of drug-induced altered consciousness.