Psilocybin Modulates TPJ Effective Connectivity during Out-of-Body Experiences

Abstract

Abstract Serotonergic psychedelics alter self-boundaries and can induce out-of-body experiences (OBEs)—the sense of being located outside one’s physical body. While OBEs also occur in clinical conditions and can be experimentally induced, their neural basis under psychedelics remains underexplored. In an open-label, baseline-controlled MRI study of 62 healthy adults administered psilocybin, we examined effective connectivity changes in regions implicated in clinical and induced OBEs. Spectral dynamic causal modelling (spDCM) was applied to resting-state and music-listening scans to estimate connectivity changes from baseline and assess their consistency across contexts. Participants were grouped by self-reported OBE symptom intensity at the end of the dosing day. In those reporting high-intensity OBEs, psilocybin reduced effective connectivity from the right to left anterior insula and between the right anterior insula and right temporoparietal junction (TPJ), inhibiting these connections across both scan types. These changes parallel known disruptions in TPJ–insula circuits linked to OBEs in clinical and experimental settings, particularly in the right hemisphere. Our findings highlight how psilocybin-induced disembodiment corresponds to altered effective connectivity and demonstrate the utility of spDCM for mapping causal neural dynamics underlying bodily self-consciousness.