A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.
A neurobiologically realistic computational model of whole-brain haemodynamic signals, perturbed to simulate loss of consciousness, reveals two distinct neurobiological paths to unconscious brain activity. Incorporating PET data on GABA receptor distribution shows that spatially-specific local inhibition reproduces fMRI activity observed during propofol anaesthesia. Incorporating diffusion MRI data from patients with disorders of consciousness shows that randomized neuroanatomical connectivity can also produce the dynamics characteristic of loss of consciousness. The results generalize across anaesthesia and injury datasets, suggesting that increased inhibition and connectome perturbation are distinct routes to the same functional brain dynamics.