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

Background: Psilocybin is a widely studied psychedelic substance, which 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 under-characterized as 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 six minutes in eyes open resting state during the peak subjective drug effect (102 minutes post-treatment) in ultra-high field 7T MRI. The 5D-ASC Rating Scale was administered 360 minutes after drug intake.

Results: Under psilocybin, there were alterations across all dimensions of the 5D-ASC scale, and widespread increases in averaged brain functional connectivity. Further time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neuro-experiential 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 both at the brain and at the experiential level. 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, providing insights into the neurophysiology and neuro-experiential qualities of the psychedelic state.