Disturbance of the sense of self may be a core marker of schizophrenia. In patients with first-episode schizophrenia-spectrum disorders compared with healthy controls, self-agency experience was associated with reduced cortical activation in the medial frontal gyrus and posterior cingulate gyrus. The ability to judge whether an action is one's own or another's depends on anti-correlated switching between the default mode and central-executive networks, a mechanism substantially impaired in the patient group during the task.
The psychedelic phenethylamine 2C-B produces less dysphoria and subjective impairment than the tryptamine psilocybin. In 22 healthy volunteers, 7 Tesla resting-state functional MRI mapped acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin, and placebo. Both compounds selectively reduced intranetwork static functional connectivity while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B showed less pronounced reductions in between-network dynamic connectivity variability but elevated transmodal static connectivity. Both increased brain complexity similarly. PET density modeling linked neural effects to differences in monoaminergic transporter and serotonergic receptor binding beyond 5-HT2A. Behavioral markers of psychedelic effects reflected decoupling of the transmodal axis of functional brain organization.