Ketamine infusion therapy can rapidly relieve depression, but its effects on whole-brain functional connections are not well understood. In patients with major depressive disorder (MDD), baseline resting-state functional connectivity (FC) differed from healthy controls in the somatomotor network and between association and default mode networks. After one and four ketamine infusions, these disrupted FC patterns trended toward those of controls. Serial ketamine treatment significantly decreased FC between the cerebellum and the salience network. Patients who remitted showed higher pre-treatment FC between the cerebellum and striatum that decreased after treatment, while non-remitters showed the opposite pattern. Ketamine induces neurofunctional plasticity in cortico-striatal-cerebellar loops involving the salience network, which may serve as a biomarker for treatment response.
Ketamine infusions alter brain connectivity in people with major depressive disorder, particularly in circuits involving the habenula and nucleus accumbens, which are linked to reward processing. After four infusions, changes in functional connections between these regions and visual, parietal, and cerebellar areas correlated with improvements in mood and anhedonia. For example, decreased variability in connectivity between the left habenula and right precuneus/visual cortex was associated with better mood, while altered connectivity between the left habenula and visual/parietal cortices and between the left nucleus accumbens and visual/parietal cortices correlated with reduced anhedonia. No such changes occurred in healthy controls.