Ketamine produces different brain oscillations in distinct regions: gamma oscillations in prefrontal cortex and hippocampus, linked to antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, linked to dissociative effects. By analyzing intracranial recordings from humans and comparing effects with propofol, the authors identified that these frequency-dependent patterns arise from distinct neural circuits, potentially guiding development of biomarkers and treatments for depression.
A subanesthetic dose of ketamine increases gamma oscillations in the prefrontal cortex and hippocampus, brain areas linked to its rapid antidepressant effects, and produces a 3 Hz oscillation in the posteromedial cortex that may underlie its dissociative effects. By adding propofol, which blocks NMDA-mediated disinhibition and shares HCN1 inhibition with ketamine, the study distinguished brain dynamics caused by NMDA-mediated disinhibition from those caused by HCN1 inhibition. The results suggest ketamine engages distinct neural circuits in frequency-dependent patterns to produce antidepressant and dissociative effects, potentially guiding development of new depression therapies with fewer side effects.