Concurrent assessment of neurometabolism and brain hemodynamics to characterize the functional brain response to psychotropic drugs: An S-ketamine study.

A new method combining two brain imaging techniques—pharmacological MRI and pharmacological MRS—was tested in 32 healthy adults given S-ketamine or placebo. S-ketamine caused strong blood-flow changes in frontal, cingulate, and insular brain regions, which matched patterns of glutamate and opioid receptors and correlated with participants' reports of dissociation. These blood-flow changes occurred alongside increases in brain glutamate and lactate, especially at higher doses. Combining both imaging methods improved the ability to predict whether a person had received placebo, a low dose, or a high dose of S-ketamine. The findings show that simultaneously measuring blood flow and brain chemistry provides complementary insights into how drugs affect the brain.

Study at a glance

Abstract

Neuroimaging techniques offer valuable insights for understanding pharmacological treatment effects in neuropsychiatric disorders. Here, we present a novel approach that simultaneously assesses hemodynamic and neurometabolic brain responses to psychotropic drugs using interleaved pharmacological magnetic resonance imaging (phMRI) and pharmacological magnetic resonance spectroscopy (phMRS). This method was tested using a double-dose, placebo-controlled, randomized, crossover design using S-ketamine as the pharmacological agent. We acquired 7 Tesla phMRI and phMRS data to evaluate time- and dose-dependent effects of S-ketamine in 32 healthy controls. S-ketamine elicited robust phMRI responses in the dorsofrontal, cingulate, and insular cortices, which correlated with glutamate and opioid receptor maps and subjective dissociation scores. These hemodynamic changes were paralleled by increases in glutamate and lactate, especially at higher doses. Furthermore, accuracy in predicting received condition (placebo, a low, or a high S-ketamine dose) increased when combining both techniques. Here, we show for the first time that concurrent phMRI and phMRS assessments provide important complementary insights into the functional brain response to pharmacological interventions.