Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action
PLoS ONE September 24, 2012 Milan Scheidegger, Martin Walter, Mick Lehmann et al. 282 citations
Ketamine, an NMDA receptor antagonist that modulates glutamate signaling, rapidly reduces functional connectivity between the default mode network (DMN) and the dorsal nexus, a dorsal medial prefrontal cortex region linked to depression. In a randomized, placebo-controlled, double-blind, crossover resting-state fMRI study in healthy subjects, ketamine decreased connectivity from the DMN's posterior cingulate cortex hub to the dorsal nexus, pregenual anterior cingulate, and medioprefrontal cortex. This subacute modulation at 24 hours overlaps with ketamine's peak antidepressant efficacy in treatment-resistant depression, suggesting that targeting glutamatergic system-driven network dysconnectivity may underlie successful depression treatment.