Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin

Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns ('functional brain networks'), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in "magic mushrooms". We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.Canadian Institutes of Health Research, Canadian Centennial Scholarship Fund and the Mann Senior Scholarship from Hertford College, University of Oxford. JC is supported by the Portuguese Foundation for Science and Technology and by the project FronThera NORTE-01-0145-FEDER-000023 from the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (FEDER). Dr. PE acknowledges support from the EPSRC award EP/N014529/1 funding the EPSRC Centre for Mathematics of Precision Healthcare at Imperial. MLK and SA are supported by the ERC Consolidator Grant CAREGIVING (n. 615539). MLK is also supported by the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). G.D. is supported by the Spanish Research Project PSI2016-75688-P (AEI/FEDER) and by the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2). RCH is supported by the Alex Mosley Charitable Trust, Ad Astra Chandaria Foundation and Tamas Foundation. The authors are grateful to the Beckley Foundation for funding the original research study, on which Amanda Feilding, Director of the Beckley Foundation, was a vital initiator and collaborative partne