Ketamine induces time-varying high-order EEG connectivity shifts tied to symptom relief in older adults with treatment-resistant depression

Researchers at Texas A&M, collaborating with Baylor College of Medicine and the University of the Balearic Islands, recorded high-density EEG before and after intravenous ketamine in older adults. They applied information-theoretic measures of high-order interactions rather than pairwise coherence to track how information organization evolved at one hour, 24 hours, and seven days. Distinct patterns appeared at each interval, with no single stable configuration emerging.

Greater 24-hour rises in one O-information metric correlated with larger reductions in depressive symptoms by day 7. This aligns with earlier findings from the same group showing ketamine feasibility in this age group and with meta-analyses in JAMA Psychiatry indicating rapid but variable antidepressant effects. The work highlights that clinical response may depend more on subsequent network reorganization than on the initial glutamate surge itself.

Prior observational data from NEJM on late-life depression underscore the need for biomarkers that forecast durable response. Limitations include the modest sample typical of early-phase EEG studies and the absence of a placebo-controlled arm. Next steps require a larger randomized trial with serial clinical and imaging endpoints to test whether 24-hour O-information thresholds can stratify patients for repeated dosing or combination strategies.