The neurophysiology of ketamine: an integrative review

Ketamine has multiple uses—as an anesthetic, a model of psychosis, and an antidepressant—but its physiology is complex because it acts on several sites at clinically relevant doses. This review examines ketamine's acute effects on the resting brain, moving from its pharmacology through in vitro and in vivo electrophysiology to EEG/MEG and neuroimaging studies (MRI and PET). The picture of ketamine's effects is complicated and sometimes confusing, likely due to differences in species, doses, and analytical methods. The authors suggest strategies for future research to address these issues.

Study at a glance

Abstract

The drug ketamine has been extensively studied due to its use in anaesthesia, as a model of psychosis and, most recently, its antidepressant properties. Understanding the physiology of ketamine is complex due to its rich pharmacology with multiple potential sites at clinically relevant doses. In this review of the neurophysiology of ketamine, we focus on the acute effects of ketamine in the resting brain. We ascend through spatial scales starting with a complete review of the pharmacology of ketamine and then cover its effects on in vitro and in vivo electrophysiology. We then summarise and critically evaluate studies using EEG/MEG and neuroimaging measures (MRI and PET), integrating across scales where possible. While a complicated and, at times, confusing picture of ketamine's effects are revealed, we stress that much of this might be caused by use of different species, doses, and analytical methodologies and suggest strategies that future work could use to answer these problems.