Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex.
Neuroimage April 25, 2022 Manesh Girn, Leor Roseman, Boris Bernhardt et al. 112 citations
LSD and psilocybin flatten the brain's normal hierarchical organization, reducing the functional separation between sensory and higher-order networks and increasing cross-talk between them. Analyzing two resting-state fMRI datasets, the principal gradient of cortical connectivity—which normally runs from basic sensory areas to complex association regions—was significantly compressed under both drugs compared to placebo. This flattening was driven by decreased specialization at both ends of the hierarchy: default mode and frontoparietal networks at the top, and somatomotor networks at the bottom. The findings support a proposed mechanistic model of the psychedelic state and demonstrate that macroscale connectivity gradients can be acutely altered by a pharmacological intervention.