Altered trajectories in the dynamical repertoire of functional network states under psilocybin

Brain activity can be understood as the exploration of a dynamical landscape of activity configurations over both space and time. This dynamical landscape may be defined in terms of spontaneous transitions within a repertoire of discrete metastable states of functional connectivity (FC), which underlie different mental processes. However, it remains unclear how the brain’s dynamical landscape might be changed in altered states of consciousness, such as the psychedelic state. The present study investigated changes in the brain’s dynamical repertoire in an fMRI dataset of healthy participants intravenously injected with the psychedelic compound psilocybin, which is found in “magic mushrooms”. We employed a data-driven approach to study brain dynamics in the psychedelic state, which focuses on the dominant FC pattern captured by the leading eigenvector of dynamic FC matrices, and enables the identification of recurrent FC patterns (“FC-states”), and their transition profiles over time. We found that a FC state closely corresponding to the fronto-parietal control system was strongly destabilized in the psychedelic state, while transitions toward a globally synchronized FC state were enhanced. These differences between brain state trajectories in normal waking consciousness and the psychedelic state suggest that the latter biases a global mode of functional integration at the expense of locally segregated activity in specific networks. These results provide a mechanistic perspective on subjective quality of the psychedelic experience, and further raise the possibility that mapping the brain’s dynamical landscape may help guide pharmacological interventions in neuropsychiatric disorders.