A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms

Leah M. Fleming, Daniel C. Javitt, Cameron S Carter, Joshua T. Kantrowitz, Ragy R. Girgis, Lawrence S. Kegeles, John D Ragland, Richard J Maddock, Tyler A. Lesh, Costin Tanase, James Robinson, William Z. Potter, Marlene Carlson, Melanie M. Wall, Tse Hwei Choo, Jack Grinband, Jeffrey Lieberman, John H. Krystal, Philip R. Corlett

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Ketamine is an uncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients.

Original languageEnglish (US)
Article number101739
JournalNeuroImage: Clinical
Volume22
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Functional connectivity
  • Ketamine
  • Psychosis
  • Resting state

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Fleming, L. M., Javitt, D. C., Carter, C. S., Kantrowitz, J. T., Girgis, R. R., Kegeles, L. S., Ragland, J. D., Maddock, R. J., Lesh, T. A., Tanase, C., Robinson, J., Potter, W. Z., Carlson, M., Wall, M. M., Choo, T. H., Grinband, J., Lieberman, J., Krystal, J. H., & Corlett, P. R. (2019). A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage: Clinical, 22, [101739]. https://doi.org/10.1016/j.nicl.2019.101739