Progress in the pharmacological treatment of brain disorders is in part hampered by the lack of neuroimaging methods that can non-invasively assess the brain’s response to such medication in vivo. Pharmacological magnetic resonance imaging (phMRI) has been proposed as a promising technique to accomplish this, but it is an inderect blood flow based method and therefore its measurements are often contaminated by (systemic) cardiovascular effects induced by psychotropic medication. In my project, I aim to directly assess drug-induced neuronal activity and therefore allow a more complete characterization of the brain response to psychotropic medication. To this end, I developed an interleaved MR protocol combining phMRI with Magnetic Resonance Spectroscopy (MRS). MRS can directly measure neurometabolites, such as the main neurotransmitters in the brain, glutamate and GABA, reflecting the excitatory-inhibitory balance in neuronal output. Therefore, incorporating MRS measurements allows us to determine the contribution of neuronal effects to the phMRI signal. We are testing this protocol in healthy volunteers using a double-dose, placebo-controlled randomized cross-over study with ketamine, a rapid-acting antidepressant that directly targets glutamate and GABA.