Background: Ketamine provides rapid antidepressant response in those struggling with major depressive disorder (MDD). This study measured acute changes in brain activity over 24 hours after a single infusion of ketamine using arterial spin labeled (ASL) functional magnetic resonance imaging (fMRI) in patients with MDD. ASL is a novel technique that provides quantitative values to measure cerebral blood flow (CBF).
Methods: A single sub-anesthetic dose (0.5 mg/kg) of ketamine was delivered intravenously. Treatment-refractory patients (n=11) were assessed at: Baseline (pre-infusion), and approximately 1hr, 6hrs, and 24hrs post-infusion. Linear mixed-effects models detected changes in CBF with respect to treatment outcome, and results were corrected for false discovery rate (FDR).
Results: After ketamine infusion, increased CBF was observed in the thalamus, while decreased CBF was observed in lateral occipital cortex in all patients. Time-by-response interactions were noted in ventral basal ganglia and medial prefrontal cortex, where CBF change differed according to antidepressant response.
Limitations: Modest sample size is a limitation of this pilot study; strict statistical correction and visualization of single-subject data attempted to ameliorate this issue.
Conclusion: In this pilot study, a sub-anesthetic dose of ketamine was associated with acute neurofunctional changes that may be consistent with altered attention, specifically increased thalamus activity coupled with decreased cortical activity. By contrast, antidepressant response to ketamine was associated with changes in reward-system regions, specifically ventral basal ganglia and medial prefrontal cortex. Further work is needed to determine whether these results generalize to larger samples and/or serial ketamine infusions associated with longer-lasting clinical effects.
Keywords: antidepressant; arterial spin labeling; cerebral blood flow; functional magnetic resonance imaging; ketamine; treatment resistant depression.