Context-dependent structurally informed effective connectivity under psilocybin
OpenAlex – August 22, 2025
Source: OpenAlex
Summary
Mystical experiences from the hallucinogen psilocybin are directly predicted by specific brain pathway changes. Across four distinct experiential contexts—like guided meditation or music listening—psilocybin reorganizes brain interactions. Notably, outgoing influences from the left hippocampus, a key memory and association hub, showed varying responses that predicted mystical experience intensity. Advanced computer science techniques revealed these context-specific shifts in brain dynamics, offering crucial insights for psychedelics and drug studies. Understanding these mechanisms is vital for mental health research topics and could inform future digital mental health interventions.
Abstract
Abstract The extent to which anatomical connectivity constrains pharmacologically altered brain dynamics remains poorly understood. Here, we combined psilocybin administration with a structurally informed effective-connectivity model to examine how structural connectivity shapes directed inter-regional influences across experiential contexts. Using dynamic causal modeling embedded in a hierarchical empirical Bayes framework, we analyzed fMRI data acquired from a hippocampo–thalamo–cortical network during rest, guided meditation, music listening and movie viewing. Across contexts, psilocybin reorganized directed interactions while preserving structure-based scaling. Effects converged on efferents (outgoing influences) from the left hippocampus—a hub interfacing mnemonic and associative systems with the default-mode network and thalamus. Notably, the left-hippocampus-to-thalamus pathway showed a sign-reversed association with mystical-experience scores (downregulation during guided meditation and upregulation during music listening). In model-based leave-one-out cross-validation, left-hippocampal efferents predicted individual differences in mystical-experience intensity. A minimal model-free benchmark (hippocampal signal variability) also showed modest associations with mystical experience. Together, these findings link context-specific, structurally informed effective connectivity to individual differences in the acute psychedelic experience, providing a mechanistic bridge between anatomy, neurodynamics, and phenomenology.