Subanesthetic doses of ketamine, similar to those used in antidepressant studies, increase anterior theta and gamma power but decrease posterior theta, delta, and alpha power, as shown by magnetoencephalographic recordings. Dynamic causal modeling revealed a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity, with AMPA-mediated changes persisting up to 50 minutes after infusion ceased, even after perceptual distortions had ended. A decrease in gain of parietal pyramidal cells correlated with participants' self-reports of blissful state. These alterations in frontoparietal connectivity patterns may be important in generating the antidepressant response to ketamine.
Ketamine alters brain oscillations, increasing high-frequency gamma waves and reducing low-frequency alpha and theta waves. A thalamo-cortical model better explained these changes than a cortex-only model. The model showed that ketamine increases specific synaptic connections: from superficial pyramidal cells to inhibitory interneurons via AMPA and NMDA receptors, and within-layer-5 pyramidal cell gain control via GABA-A and NMDA receptors. Receptor time-constants remained unchanged. These findings support using generative models to understand oscillatory data and provide computational evidence that ketamine alters local neural coupling through multiple neurotransmitter systems.