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

Neuroimage Clin. 2019:22:101739. doi: 10.1016/j.nicl.2019.101739. Epub 2019 Feb 28.

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.

Keywords: Functional connectivity; Ketamine; Psychosis; Resting state.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Excitatory Amino Acid Antagonists / adverse effects*
  • Female
  • Humans
  • Ketamine / adverse effects*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging*
  • Nerve Net / drug effects
  • Schizophrenia / chemically induced*
  • Schizophrenia / diagnostic imaging*
  • Young Adult

Substances

  • Excitatory Amino Acid Antagonists
  • Ketamine