Talk by Prof. Dr. Ulrich Ettinger (University of Bonn)
Effects of Ketamine on Cognition and Brain Function
In this talk I will present findings from recent investigations into the effects of ketamine on cognition, oculomotor control and brain function. Ketamine has been proposed to model symptoms of psychosis. Support for this hypothesis comes from studies that report ketamine-induced alterations in cognition and brain function that resemble the deficits observed in schizophrenia. Here, I will focus on well-established biomarkers and endophenotypes of schizophrenia spectrum disorders, viz. smooth pursuit eye movements (SPEM) and antisaccades (AS), as well as other measures of cognitive function. We and others have observed SPEM impairments during ketamine administration in healthy volunteers. These appear to resemble the deficits observed in schizophrenia, but cannot be prevented with antipsychotic pre-dosing in healthy participants. Antisaccade performance, in contrast, appears to be relatively uninfluenced by ketamine administration. This finding is surprising, given that antisaccade error rates are reliably and robustly increased in schizophrenia patients, and reflects a limitation of the ketamine model of psychosis. In a recent study, we investigated the neural effects of ketamine during SPEM and AS in healthy participants using functional magnetic resonance imaging (fMRI) at 3T. In agreement with previous studies, ketamine administration induced psychosis-like symptoms and led to robust deficits in SPEM performance, accompanied by reduced blood oxygen level dependent (BOLD) signal in the SPEM network compared to placebo. These results bear resemblance to the deviations found in schizophrenia patients. In contrast, AS error rate and BOLD response during the AS task were largely unaffected by ketamine. Overall, our findings support the role of glutamate in SPEM and provide partial support for the use of ketamine as a pharmacological model of psychosis.