Effective connectivity of emotion and cognition under psilocybin

Classic psychedelics alter sense of self and patterns of self-related thought. These changes are hypothesised to underlie their therapeutic efficacy across internalising pathologies such as addiction and depression. Using resting-state functional MRI images from a randomised, double blinded, placebo-controlled clinical trial of 24 healthy adults under 0.215mg/kg psilocybin, we investigated how psilocybin modulates the effective connectivity between resting state networks and the amygdala that are involved in the appraisal and regulation of emotion and association with clinical symptoms. The networks included the default mode network (DMN), salience network (SN) and central executive network (CEN). Psilocybin decreased top-down effective connectivity from the resting state networks to the amygdala and decreased effective connectivity within the DMN and SN, while the within CEN effective connectivity increased. Effective connectivity changes were also associated with altered emotion and meaning under psilocybin. Our findings identify changes to cognitive-emotional connectivity associated with the subjective effects of psilocybin and the attenuation of the amygdala signal as a potential biomarker of psilocybin’s therapeutic efficacy. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03736980 ### Funding Statement Heffter Research Institute (Grant No. 1- 190420) Swiss Neuromatrix Foundation (Grant No. 2016-0111) Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908), Slovenian Research Agency (ARRS) (Grant Nos. J7-8275, J7-6829, and P3-0338 [to GR]) Council Discovery Early Career Research Award Fellowship DE170100128 (to AR) Australian Research Council Discovery Project grant DP200100757 (AR) Australian National Health and Medical Research Council Investigator grant 1194910 (AR) Wellcome Centre for Human Neuroimaging supported by core funding from Wellcome grant 203147/Z/16/Z (AR) ### 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 data analysed in this paper were collected as part of a previous study (registered at ClinicalTrials.gov ([NCT03736980][1])), which is reported in (Katrin H. Preller et al., 2020, doi: 10.1016/j.biopsych.2019.12.027) and was approved by the Cantonal Ethics Committee of Zurich. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03736980&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F06%2F2022.09.06.22279626.atom