A Meta-Analysis of Functional Neuroimaging Studies of Ketamine Administration in Healthy Volunteers

Ketamine administration leads to a psychotomimetic state when taken in large bolus doses, making it a valid model of psychosis. Therefore, understanding ketamine's effects on brain functioning is particularly relevant. This meta-analysis focused on neuroimaging studies that examined ketamine-induced brain activation at rest and during a task. Included are 10 resting-state studies and 23 task-based studies, 9 of which were measuring executive functions. Using a stringent statistical threshold (TFCE <0.05), the results showed increased activity at rest in the dorsal anterior cingulate cortex (ACC), and increased activation of the right Heschl's gyrus during executive tasks, following ketamine administration. Uncorrected results showed increased activation at rest in the right (anterior) insula and the right-fusiform gyrus, as well as increased activation during executive tasks in the rostral ACC. Rest-state studies highlighted alterations in core hubs of the salience network, while task-based studies suggested an impact on task-irrelevant brain regions. Increased activation in the rostral ACC may indicate a failure to deactivate the default mode network during executive tasks following ketamine administration. The results are coherent with alterations found in schizophrenia, which confer external validity to the ketamine model of psychosis. Studies investigating the neural mechanisms of ketamine's antidepressant action are warranted.