Ketamine and psilocybin, two drugs with therapeutic potential for depression, produce distinct effects on brain electrical activity. Ketamine disrupts the balance between excitation and inhibition in neural circuits, as shown by changes in the aperiodic components of EEG spectra, and reduces beta band activity. Psilocybin also reduces alpha power in similar brain regions but does not affect beta activity or aperiodic components in the same way. These differences reflect their different mechanisms: ketamine blocks NMDA receptors while psilocybin targets serotonin receptors. Ketamine's unique EEG signature supports its role as a model for prodromal psychosis.
Ketamine and psilocybin affect sensory learning in the brain through different neural mechanisms. By combining computational modeling with EEG data from a previous study, researchers analyzed how these drugs alter the brain's processing of prediction errors during an auditory task. Ketamine produced a larger reduction in sensory precision from 207 to 316 milliseconds after sounds, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect on this measure. Both drugs reduced belief precision between 160 to 184 milliseconds, peaking at 172 milliseconds. For higher-level volatility prediction errors, ketamine reduced expression while psilocybin had no effect at 312 milliseconds. These distinct effects could inform tailored therapies for major depressive disorder.