Critical Evaluation of “Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks” (Jiang et al., 2026)

The evaluation finds Jiang et al.’s study to be a scientifically rigorous and methodologically advanced investigation into how psilocybin reshapes brain connectivity. Using viral tracing, imaging, and electrophysiology, the authors show that psilocybin induces long-lasting, network-specific synaptic changes in the mouse brain, strengthening inputs from sensory and association areas to subcortical-projecting frontal neurons, while weakening cortico-cortical loops. The rewiring is activity-dependent and may underlie the drug’s therapeutic effects by promoting flexible information flow. The study is well-controlled, accurately interpreted, and offers significant translational insight, establishing a credible neural mechanism for the lasting psychological benefits observed in psychedelic therapy.