Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex
bioRxiv (Cold Spring Harbor Laboratory) May 3, 2020 Manesh Girn, Leor Roseman, Boris C. Bernhardt et al. 27 citations preprint
LSD and psilocybin flatten the brain's hierarchical organization, reducing the functional separation between sensory and higher-order cognitive networks. Using a non-linear dimensionality reduction technique on resting-state fMRI data, the authors found that both drugs compressed the principal gradient of cortical connectivity, which normally spans from unimodal (sensory) to transmodal (association) cortex. This flattening was driven by decreased differentiation at both ends of the hierarchy—default and frontoparietal networks at the upper end and somatomotor networks at the lower end—and was accompanied by increased crosstalk between unimodal and transmodal regions. Changes in the principal gradient under LSD tracked self-reported ego-dissolution. The findings support a mechanistic model of the psychedelic state and demonstrate that macroscale connectivity gradients are sensitive to serotonergic modulation.