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Randomized Controlled Trial
. 2015 Apr 19;18(9):pyv040.
doi: 10.1093/ijnp/pyv040.

Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia

Anna Höflich  1 , Andreas Hahn  1 , Martin Küblböck  1 , Georg S Kranz  1 , Thomas Vanicek  1 , Christian Windischberger  1 , Alois Saria  1 , Siegfried Kasper  1 , Dietmar Winkler  1 , Rupert Lanzenberger  2
Affiliations
Randomized Controlled Trial

Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia

Anna Höflich et al. Int J Neuropsychopharmacol. .

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.

Keywords: functional MRI; glutamate; ketamine; schizophrenia; thalamus.

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Figures

Figure 1.
Figure 1.
Ketamine effects on functional connectivity of the thalamus hub network (analysis 1). Each period of 2.5 minutes is depicted. Interaction effects drug*time of posthoc t tests are displayed and data overlaid on a standard-MNI brain. Warm colors stand for increase of connectivity and cold colors for decreased connectivity, while color intensity refers to t-values (range t=3.09…6). A significant increase is shown in temporo-parietal regions throughout the ketamine application. x=-58mm, y=-16mm.
Figure 1.
Figure 1.
Ketamine effects on functional connectivity of the thalamus hub network (analysis 1). Each period of 2.5 minutes is depicted. Interaction effects drug*time of posthoc t tests are displayed and data overlaid on a standard-MNI brain. Warm colors stand for increase of connectivity and cold colors for decreased connectivity, while color intensity refers to t-values (range t=3.09…6). A significant increase is shown in temporo-parietal regions throughout the ketamine application. x=-58mm, y=-16mm.
Figure 2.
Figure 2.
Ketamine-induced alterations of cortic-thalamic functional connectivity (analysis 2). Posthoc t tests of the interaction drug*time show a significant increase of functional connectivity for the somatosensory (left row) and temporal cortex (right row). Other regions without significant results are not shown. Results of seed-to-voxel correlation analysis are overlaid onto a single-subject standard brain (range of t-values=3.09…6). Results are shown for each period of 2.5 minutes. z=7mm.
Figure 3.
Figure 3.
Graphical representation of study design, resting-state fMRI protocol, and the application of the study drug.
See this image and copyright information in PMC

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