Emotionalcognitive processing and brain metabolism after pharmacological challenge with ketamine

Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties, thus providing a valuable research tool for the investigation of the neurobiology of major depressive disorder (MDD). Increasing evidence underscores the role of glutamate dependent neuroplasticity and glutamatergic neurotransmission and metabolism in the pathophysiology of MDD. This multimodal imaging study in 23 healthy subjects aimed at probing the neuropharmacological effects of a single ketamine infusion on fMRI-BOLD responses during emotional/cognitive processing and their relationship to glutamatergic metabolite concentrations assessed by proton magnetic resonance spectroscopy (1H-MRS). During emotional processing there was a brain region-specific increase in negative BOLD responses (NBRs) following ketamine administration. The most significant BOLD differences were found in predominantly limbic brain areas associated with the processing of emotional information and higher-order mental functions. During cognitive processing there was a significant ketamine effect on NBRs in anterior, but not posterior regions of the default- mode network. A strong correlation between glutamate, glutamine, GABA as well as glutamine/glutamate ratios (a putative marker for glutamatergic neurotransmission) and NBRs could be found after ketamine administration.