High-order brain interactions during ketamine-induced state changes: A functional marker of response in late-life treatment-resistant depression?
Translational Psychiatry July 4, 2026 Krisha Shah, Rubén Herzog, Alan C. Swann et al.
Ketamine rapidly reduces depression in some people with treatment-resistant depression, but the brain mechanisms are not fully understood. This analysis of a randomized, double-blind trial compared ketamine to midazolam in 30 older veterans with treatment-resistant depression. Using EEG data and a measure called O-information, which captures how brain regions interact in groups of three or more, the study found that ketamine caused dynamic changes in these interactions over time. The strongest effects occurred in alpha brain waves one hour after infusion, with changes shifting to theta waves by 24 hours and partially returning in beta and gamma waves by day 7.