GesundEuropan Campus Rottal-Inn
M. Steffens, C. Neumann, Anna-Maria Kasparbauer, B. Becker, B. Weber, M. Mehta, R. Hurlemann, U. Ettinger
Effects of ketamine on brain function during response inhibition
Psychopharmacology, vol. 235, pp. 3559-3571
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.
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.
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.
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.
GesundEuropan Campus Rottal-Inn
M. Steffens, B. Becker, C. Neumann, Anna-Maria Kasparbauer, I. Meyhöfer, B. Weber, M. Mehta, R. Hurlemann, U. Ettinger
Effects of Ketamine on Brain Function During Smooth Pursuit Eye Movements
Human Brain Mapping, vol. 37, no. 11, pp. 4047-4060
The uncompetitive NMDA receptor antagonist ketamine has been proposed to model symptoms of psychosis. Smooth pursuit eye movements (SPEM) are an established biomarker of schizophrenia. SPEM performance has been shown to be impaired in the schizophrenia spectrum and during ketamine administration in healthy volunteers. However, the neural mechanisms mediating SPEM impairments during ketamine administration are unknown. In a counter‐balanced, placebo‐controlled, double‐blind, within‐subjects design, 27 healthy participants received intravenous racemic ketamine (100 ng/mL target plasma concentration) on one of two assessment days and placebo (intravenous saline) on the other. Participants performed a block‐design SPEM task during functional magnetic resonance imaging (fMRI) at 3 Tesla field strength. Self‐ratings of psychosis‐like experiences were obtained using the Psychotomimetic States Inventory (PSI). Ketamine administration induced psychosis‐like symptoms, during ketamine infusion, participants showed increased ratings on the PSI dimensions cognitive disorganization, delusional thinking, perceptual distortion and mania. Ketamine led to robust deficits in SPEM performance, which were accompanied by reduced blood oxygen level dependent (BOLD) signal in the SPEM network including primary visual cortex, area V5 and the right frontal eye field (FEF), compared to placebo. A measure of connectivity with V5 and FEF as seed regions, however, was not significantly affected by ketamine. These results are similar to the deviations found in schizophrenia patients. Our findings support the role of glutamate dysfunction in impaired smooth pursuit performance and the use of ketamine as a pharmacological model of psychosis, especially when combined with oculomotor biomarkers.