Fig. 1: Model of effective connectivity change from placebo to psilocybin.

A Estimated mean effective connectivity 70 min post-administration of placebo, (B) estimated change to effective connectivity from placebo to psilocybin and (C) estimated mean effective connectivity 70 minutes post-administration of psilocybin. Brain regions – Early Visual Area (EVA), Fusiform Gyrus (FG), Inferior Frontal Gyrus (IFG), Intraparietal Sulcus (IPS). Cool colours represent inhibition; warm colours represent excitation. For self-connections only, a positive value indicates a move away from excitation, and is represented here as a cool coloured to indicate increased inhibition. Panel (A) displays placebo mean effective connectivity (EC) for reference. Panel (B) shows change from placebo EC which takes into account EC estimates of placebo and psilocybin, 70 min post administration to provide posterior expectations (see Supplementary Fig 3 (A) and (B)). These estimations of EC change from placebo to psilocybin reinforce the general trend of mean EC findings and are displayed to aid visualisation of the connectivity changes induced by psilocybin. Unlike mean EC of the group at (A) placebo and (C) under psilocybin, change in posterior expectation is calculated by using the posterior means of EC of both conditions but calculated as the Bayesian model average at the group level taken over the two conditions. Panel (C) displays mean EC changes under psilocybin. Self-inhibition of the EVA, FG, IFG and IPS was found. Panel (B) reaffirmed the EVA, FG and IFG self-inhibition. Excitation from the EVA to IFG was absent in psilocybin mean EC (Panel (C)) and can be explained by the inhibitory change displayed in panel (B). The strong inhibitory connectivity estimated from the IFG to the FG was diminished. Inhibition is demonstrated across all efferent connections except the FG, which remained at similar effective size values (posterior expectations) under placebo and psilocybin. Panel (C) also demonstrates behavioural associations to mean EC, 70 min post administration of psilocybin and indicates the direction of EC change found under psilocybin. Behavioural scores were measured on a shortform 5D-ASC in-scanner, immediately after scans. A positive behavioural association, indicated by a red value, means the behavioural variable tends to increase when the EC moves in the excitatory direction. Conversely, a negative association, indicated by a blue value, means the behavioural variable tends to decrease when the EC moves in the excitatory direction. Values for EI = elemental imagery, CI = complex imagery, D = disembodiment and U = experience of unity are displayed. The effect sizes (i.e., the posterior expectations) of connections are in Hz except self-connections which are modelled as always inhibitory and are log-scaled (see Supplementary material for more details). Behavioural associations and connections displayed are estimated at posterior probability >0.99, which amounts to very strong evidence. For results inclusive of posterior probability >0.50, see Supplementary Fig S2.