Two hours after a single intravenous dose of ketamine (0.8 mg/kg over 50 minutes), healthy adults showed a reduction in the ratio of GABA to total creatine in the hippocampus, as measured by magnetic resonance spectroscopic imaging. No significant changes were observed in the glutamate-plus-glutamine ratio or the GABA-to-glutamate-plus-glutamine ratio across seven brain regions. Plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were not significantly associated with changes in any neurotransmitter ratio. The findings suggest that ketamine may alter GABA turnover in the hippocampus, a region relevant to its emerging antidepressant effects.
Negative fMRI signals in the brain's default mode network (DMN) during cognitive control do not reflect a relative increase in synaptic activity during rest periods. Using hybrid PET-MRI, the study found that task-positive BOLD responses in attention and control networks align with increased glucose metabolism during cognitive control, but metabolism in the DMN remained high during both rest and task despite negative BOLD responses. This dissociation indicates that DMN BOLD responses are not simply the inverse of metabolic activity, challenging common interpretations and suggesting distinct neurovascular coupling in this network.