Healthy VolunteersSchizophreniaKetamine

Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

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.

Authors

  • Siegfried Kasper

Published

International Journal of Neuropsychopharmacology
individual Study

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.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topics
  • Author
  • APA Citation

    Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., Saria, A., Kasper, S., Winkler, D., & Lanzenberger, R. (2015). Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. International Journal of Neuropsychopharmacology, 18(9), pyv040. https://doi.org/10.1093/ijnp/pyv040

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