Deep brain stimulation modulates directional limbic connectivity in major depressive disorder

Deep brain stimulation (DBS) is being investigated as treatment for patients with refractory major depressive disorder (MDD). However, little is known about how DBS exerts its antidepressive effects. Here, we investigated whether ventral anterior limb of the internal capsule (vALIC) stimulation modulates a limbic network centered around the amygdala in patients with treatment resistant MDD. Nine patients underwent resting state functional magnetic resonance imaging (fMRI) before DBS surgery and after one year of treatment. In addition, they were scanned twice within two weeks during the subsequent double blind crossover phase with active and sham treatment. Eleven matched controls underwent fMRI scans at same time intervals to account for test-retest effects. The imaging data was investigated with functional connectivity analysis and dynamic causal modelling (DCM). Results showed that one year of DBS treatment was associated with increased functional connectivity of the left amygdala with precentral cortex and left insula along with decreased bilateral connectivity between nucleus accumbens and ventromedial prefrontal cortex. No changes in functional connectivity were observed during the crossover phase. Effective connectivity analyses using DCM revealed widespread amygdala-centric changes between pre-surgery and one year follow-up, while the crossover phase was associated with insula-centric changes between active and sham stimulation. These results suggest that vALIC DBS results in complex rebalancing of the limbic network involved in emotion, reward and interoceptive processing.