Ketamine modulates hippocampal neurochemistry and functional connectivity: a combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers (original) (raw)

2016, Molecular Psychiatry

A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-daspartate 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 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 of hippocampal Glx (glutamate+glutamine; F= 3.76; p= 0.04), a decrease in frontotemporal (t=4.92, p FDR < .05, k E = 2198, x=-30, y= 52, z= 14) and temporo-parietal functional connectivity (t=5.07, p FDR < .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. Keywords schizophrenia; Glx (glutamate+glutamine); N-methyl-d-aspartate receptor (NMDAR); GABA; psychosis; fronto-temporal; temporo-parietal Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: