Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans
Journal of Neuroscience – August 19, 2015
Source: OpenAlex
Summary
Ketamine's antidepressant effects are associated with profound, sustained alterations in brain connectivity. Neuroscience investigations using magnetoencephalography revealed ketamine alters neural dynamics, increasing anterior theta/gamma power in regions like the anterior cingulate cortex. Crucially, it reduced NMDA and AMPA receptor-mediated frontoparietal connectivity. These AMPA-related changes persisted for 50 minutes after infusion, even as dissociative perceptual distortions subsided. Decreased parietal cell gain correlated with reported blissful states, suggesting these functional brain connectivity shifts are key to the Treatment of Major Depression.
Abstract
In this paper, we found that 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 revealed by magnetoencephalographic recordings. Dynamic causal modeling of frontoparietal connectivity changes with ketamine indicated a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity. AMPA-mediated connectivity changes were sustained for up to 50 min after ketamine infusion had ceased, by which time perceptual distortions were absent. The results also indicated a decrease in gain of parietal pyramidal cells, which was correlated with participants' self-reports of blissful state. The alterations in frontoparietal connectivity patterns we observe here may be important in generating the antidepressant response to ketamine.