Psychedelics appear to temporarily increase cross talk between large-scale brain networks. An international mega-analysis of 11 resting-state fMRI datasets in Nature Medicine found stronger connectivity between higher-order association systems, such as the default mode and frontoparietal networks, and sensory or motor networks including visual, somatomotor, and attention systems.
This pattern points to a reconfiguration rather than a simple shutdown of the default mode network. Normally segregated systems communicate more during the acute drug state, and subcortical structures like thalamus, caudate, putamen, and cerebellum also show altered coupling with sensorimotor networks.
Decreases within networks were observed too, especially inside sensory and motor systems, but these effects were less widespread and less robust than the between-network increases. Psilocybin and LSD showed similar patterns; DMT appeared stronger, mescaline partly overlapped, and ayahuasca diverged more, though the latter findings were based on smaller datasets. These results describe acute brain activity and do not establish therapeutic mechanisms.
In short, psychedelics transiently reshuffle how brain networks communicate.