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.
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.
Papers in Blossom that reference this study
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Prugger, J., Derdiyok, E., Dinkelacker, J. et al. · Scientific Data (2022)
Dourron, H. M., Strauss, C., Hendricks, P. S. · Pharmacological Reviews (2022)
Li, D., Vlisides, P. E., Mashour, G. A. · NeuroImage (2022)
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