Working memory deficits in disorders like schizophrenia may stem from disrupted brain cell tuning. Using fMRI, researchers found that ketamine, which blocks NMDA receptors, broadens neural spatial tuning in healthy people, reducing the precision of brain responses across visual, parietal, and frontal areas and worsening spatial working memory accuracy. These tuning changes were more consistent across individuals and brain regions than overall activation changes and correlated with memory performance. The results link NMDA receptor disruption to altered brain circuit dynamics and memory impairment, offering a target for developing treatments.
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.