Journal Article

Effects of ketamine on brain function during response inhibition

Neumann, C., Hurlemann, R., Ettinger, U., Kasparbauer, A.-M., Mehta, M. A., Steffens, M., Becker, B., Weber, B.

2018

Overview

Introduction The uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist ketamine has been proposed to model symptoms of psychosis. Inhibitory deficits in the schizophrenia spectrum have been reliably reported using the antisaccade task. Interestingly, although similar antisaccade deficits have been reported following ketamine in non-human primates, ketamine-induced deficits have not been observed in healthy human volunteers. Methods To investigate the effects of ketamine on brain function during an antisaccade task, we conducted a double-blind, placebo-controlled, within-subjects study on n  = 15 healthy males. We measured the blood oxygen level dependent (BOLD) response and eye movements during a mixed antisaccade/prosaccade task while participants received a subanesthetic dose of intravenous ketamine (target plasma level 100 ng/ml) on one occasion and placebo on the other occasion. Results While ketamine significantly increased self-ratings of psychosis-like experiences, it did not induce antisaccade or prosaccade performance deficits. At the level of BOLD, we observed an interaction between treatment and task condition in somatosensory cortex, suggesting recruitment of additional neural resources in the antisaccade condition under NMDAR blockage. Discussion Given the robust evidence of antisaccade deficits in schizophrenia spectrum populations, the current findings suggest that ketamine may not mimic all features of psychosis at the dose used in this study. Our findings underline the importance of a more detailed research to further understand and define effects of NMDAR hypofunction on human brain function and behavior, with a view to applying ketamine administration as a model system of psychosis. Future studies with varying doses will be of importance in this context.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Administration, Intravenous / Adult / Biomedical and Life Sciences / Biomedicine / Blindness / Brain / Brain - diagnostic imaging / Brain - drug effects / Brain - physiology / Dosage and administration / Double-Blind Method / Excitatory Amino Acid Antagonists - administration & dosage / Excitatory Amino Acid Antagonists - adverse effects / Eye Movements - drug effects / Eye Movements - physiology / Glutamic acid receptors (ionotropic) / Humans / Intravenous administration / Ketamine / Ketamine - administration & dosage / Ketamine - adverse effects / Localization of functions / Magnetic resonance imaging / Male / Mental disorders / N-Methyl-D-aspartic acid receptors / Neurosciences / Original Investigation / Pharmacology/Toxicology / Photic Stimulation - methods / Physiological aspects / Psychiatry / Psychosis / Reaction Time - drug effects / Reaction Time - physiology / Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors / Receptors, N-Methyl-D-Aspartate - physiology / Saccadic eye movements / Schizophrenia / Schizophrenia - chemically induced / Schizophrenia - physiopathology / Somatosensory cortex / Young Adult