Ketamine modulates hippocampal neurochemistry and functional connectivity: A combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers

Academic Article


  • A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-d-aspartate receptor (NMDAR) hypofunction on γ-aminobutyric acid (GABA) interneurons disinhibiting pyramidal cells may be relevant to this hyperglutamatergic state. To better understand how NMDAR hypofunction affects the brain, we used magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging (MRI) to study the effects of ketamine on hippocampal neurometabolite levels and functional connectivity in 15 healthy human subjects. We observed a ketamine-induced increase in hippocampal Glx (glutamate+glutamine; F=3.76; P=0.04), a decrease in fronto-temporal (t=4.92, P FDR <0.05, k E =2198, x=-30, y=52, z=14) and temporo-parietal functional connectivity (t=5.07, P FDR <0.05, k E =6094, x=-28, y=-36, z=-2), and a possible link between connectivity changes and elevated Glx. Our data empirically support that hippocampal glutamatergic elevation and resting-state network alterations may arise from NMDAR hypofunction and establish a proof of principle whereby experimental modelling of a disorder can help mechanistically integrate distinct neuroimaging abnormalities in schizophrenia.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Kraguljac NV; Frölich MA; Tran S; White DM; Nichols N; Barton-Mcardle A; Reid MA; Bolding MS; Lahti AC
  • Start Page

  • 562
  • End Page

  • 569
  • Volume

  • 22
  • Issue

  • 4