Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness

Background: Psilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state's neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment. Methods: Healthy participants were randomized to receive either psilocybin (n = 22) or placebo (n = 27) and scanned for 6 minutes in an eyes-open resting state during the peak subjective drug effect (102 minutes posttreatment) in ultrahigh field 7T magnetic resonance imaging. The 5-Dimensional Altered States of Consciousness Rating Scale was administered 360 minutes after drug intake. Results: Under psilocybin, there were alterations across all dimensions of the 5-Dimensional Altered States of Consciousness Rating Scale and widespread increases in averaged brain functional connectivity. Time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low blood oxygen level–dependent signal amplitude, suggesting heightened cortical arousal. In terms of neuroexperiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness and secondly with visionary restructuralization. Conclusions: Psilocybin generates profound alterations at both the brain and the experiential levels. We suggest that the brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, thereby providing insights into the neurophysiology and neuroexperiential qualities of the psychedelic state.