Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia
Hahn, A., Höflich, A., Kasper, S., Kranz, G. S., Küblböck, M., Lanzenberger, R., Saria, A., Vanicek, T., Windischberger, C., Winkler, P.
This double-blind, randomised, placebo-controlled, within-subjects crossover study (n=30) investigated the effects of esketamine (23.1mg/70kg) on the modulation of thalamocortical circuitry during resting state in healthy volunteers, to investigate whether their brain connectivity exhibits a similar profile as patients with schizophrenia. They found that a subanesthetic dose of ketamine leads to significantly higher functional connectivity in the thalamus hub network, and the strengthening of functional cortico-thalamic connectivity for the somatosensory and temporal seed regions but not for prefrontal, occipital, and parietal regions, in accordance with the connectivity profile of schizophrenia.
Abstract
Background: Schizophrenia has been associated with disturbances of thalamic functioning. In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-D-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity.Methods: Based on the ketamine model of psychosis, we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan. Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind, randomized, placebo-controlled, crossover design.Results: Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network, more precisely, an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.Conclusions: Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists.