Dose-dependent and dynamic effects of esketamine on neurometabolism: a 7T functional MRI/MRS study

Motivation: An integrated imaging approach using functional magnetic resonance imaging (fMRI) and functional proton magnetic resonance spectroscopy (fMRS) can increase our understanding of the functional response to antidepressant medication like es-ketamine. Goal(s): We aimed to assess the dose- and time-dependent effects of the antidepressant es-ketamine on the functional brain response. Approach: We used an interleaved fMRI and fMRS experiment to assess whole-brain changes in BOLD signal and neurometabolite changes in the anterior cingulate cortex. Results: Es-ketamine increased glutamate levels and the BOLD signal, and decreased aspartate and glucose levels in the first 10-15 minutes following administration, with specific dose-dependent effects. Impact: Our results show both dose- and time-dependent neurometabolic and hemodynamic responses to es-ketamine. Understanding the contribution of these two determinants of the functional response might advance our understanding of the effects of antidepressant medication on the human brain.