Both electroconvulsive therapy (ECT) and ketamine reduce amygdala reactivity to positive and negative emotional faces in people with treatment-resistant depression. In a naturalistic study of 44 patients (17 receiving ECT, 27 receiving ketamine), fMRI showed decreased amygdala response after both treatments. Subtle differences between treatments appeared in the dorsolateral prefrontal cortex and insula. Changes in brain activity in the inferior parietal cortex correlated with overall symptom improvement, while frontal region changes correlated with anxiety for negative faces and anhedonia for positive faces. The findings suggest common and distinct neural mechanisms underlying fast-acting antidepressant effects on emotion processing.
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.