Psychedelics reduce bottom-up brain activity in the default mode network across humans and mice

Research using an optical-flow method to track moving brain activity found that several psychoactive substances reduce the magnitude of propagating waves and, in some cases, the upward flow of sensory information into the default mode network, a system involved in self-reflection. In small human studies, MDMA and LSD consistently reduced bottom-up signaling, while psilocybin produced a similar but statistically weaker directional effect. LSD produced comparable changes in mice measured with calcium imaging, supporting the interpretation that the findings reflect neural activity rather than imaging artifacts. In the MDMA study, stronger reductions in bottom-up processing were associated with impaired control and fear of ego dissolution. The results may help explain therapeutic effects in depression, but could also pose risks for people vulnerable to psychosis. The studies were small, limited to healthy participants, and focused on cortical surface activity, so larger clinical studies are needed.