Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review

Acute ketamine administration has been widely used in neuroimaging research to mimic psychosis-like symptoms. Within the last two decades, ketamine has also emerged as a potent, fast-acting antidepressant. The delayed effects of the drug, observed 2–48 h after a single infusion, are associated with marked improvements in depressive symptoms. At the systems’ level, several studies have investigated the acute ketamine effects on brain activity and connectivity; however, several questions remain unanswered around the brain changes that accompany the drug’s antidepressant effects and how these changes relate to the brain areas that appear with altered function and connectivity in depression. This review aims to address some of these questions by focusing on resting-state brain connectivity. We summarise the studies that have examined connectivity changes in treatment-naïve, depressed individuals and those studies that have looked at the acute and delayed effects of ketamine in healthy and depressed volunteers. We conclude that brain areas that are important for emotional regulation and reward processing appear with altered connectivity in depression whereas the default mode network presents with increased connectivity in depressed individuals compared to healthy controls. This finding, however, is not as prominent as the literature often assumes. Acute ketamine administration causes an increase in brain connectivity in healthy volunteers. The delayed effects of ketamine on brain connectivity vary in direction and appear to be consistent with the drug normalising the changes observed in depression. The limited number of studies however, as well as the different approaches for resting-state connectivity analysis make it very difficult to draw firm conclusions and highlight the importance of data sharing and larger future studies.