Ketamine, an NMDAR antagonist, increased oxidative metabolism (CMRO2) and cerebral blood flow in the prefrontal cortex and other cortical regions, but did not alter resting-state cortical functional connectivity or brain-wide CBF-CMRO2 coupling. Higher baseline CMRO2 was associated with lower task-related prefrontal activation and greater working memory accuracy impairment under both saline and ketamine conditions. These findings suggest that CMRO2 and resting-state functional connectivity index distinct dimensions of neural activity, and that ketamine's impairment of working memory-related neural activity and performance relates to its induction of cortical metabolic activation.
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.