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.
In major depressive disorder, ketamine infusions alter brain connectivity in networks involving the habenula and nucleus accumbens, regions central to reward processing. After four subanesthetic ketamine infusions given to 58 adults with depression, resting-state fMRI scans showed specific changes in static and dynamic functional connectivity between these regions and visual, parietal, and cerebellar areas. Decreased variability in connectivity between the left habenula and right precuneus and visual cortex, and between the right nucleus accumbens and right visual cortex, correlated with reduced depression severity. Reduced connectivity between the left habenula and visual/parietal cortices, and increased connectivity between the left nucleus accumbens and visual/parietal cortices, correlated with improvements in anhedonia. Ketamine appears to modulate overlapping habenula and nucleus accumbens functional pathways related to therapeutic response.