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

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. Competing Interest Statement The authors have declared no competing interest. Clinical Trial ACTRN12621001375842 Funding Statement This research is funded by the Australian Research Council (Refs: DE170100128 and DP200100757) and the Australian National Health and Medical Research Council (Investigator Grant 1194910). A.R. is a�liated with The Wellcome Centre for Human Neuroimaging, supported by core fund-ing from Wellcome [203147/Z/16/Z]. A.R. is a CIFAR Azrieli Global Scholar in the Brain, Mind & Consciousness Program. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Monash Uni- versity Human Research Ethics Committee. The trial was registered with the Australian New Zealand Clinical Trials Registry under the registration number ACTRN12621001375842. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors