Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

• Type of Material: Article
• Authors: Eric A. Maltbie, Emory University; Kaundinya Gopinath, Emory University; Leonard Howell, Emory University
• Language: English
• Date: 2017-12
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): https://insights.ovid.com/crossref?an=00008877-201712000-00004
• Title of Journal or Parent Work: Behavioural Pharmacology
• ISSN: 0955-8810
• Volume: 28
• Issue: 8
• Start Page: 610
• End Page: 622
• Grant/Funding Information: This research was supported by P51OD11132 (Yerkes National Primate Research Center), Sunovion Pharmaceuticals, Ltd (LLH) and DA031246 (LLH).
• Keywords: Functional connectivity; Dorsolateral prefrontal cortex; Pharmacological imaging; Ketamine infusion
• Research Categories: Health Sciences, Radiology; Psychology, Behavioral

Abstract

Ketamine has been used as a pharmacological model for schizophrenia, as sub-anesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional magnetic resonance imaging studies have revealed at a systems level focused on brain circuitry. Multiple analytic approaches show that ketamine produces robust and consistent effects at the whole-brain level. These effects are highly conserved across human and nonhuman primates, validating the use of nonhuman primate models for further investigations with ketamine. Regional analysis of brain functional connectivity suggests that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse. There are still important questions about the mechanism of action and therapeutic potential of ketamine that can be addressed using appropriate functional neuroimaging techniques.