Reward circuit function and treatment outcome following vALIC deep brain stimulation in treatment-resistant depression

Depression is associated with abnormal functioning of the reward circuit. Several deep brain stimulation (DBS) targets for treatment-resistant depression (TRD) directly modulate white matter bundles of the reward circuit. Here we investigated whether baseline reward processing in the brain is associated with ventral anterior limb of the internal capsule (vALIC) DBS outcome and whether vALIC DBS changes neural activity in the reward circuit. We studied fifteen patients with TRD who performed a monetary reward task during functional magnetic resonance imaging (fMRI) before vALIC DBS surgery, after DBS parameter optimization, and during a sham-controlled crossover phase. DBS devices were switched off during scanning for MRI safety reasons. Additionally, fifteen matched healthy controls were investigated twice to account for test-retest effects. We investigated brain responses to reward anticipation, loss anticipation, reward feedback and loss feedback. Results showed that lower baseline nucleus accumbens activation during loss anticipation and higher baseline caudate nucleus and midcingulate cortex activation during reward feedback processing were associated with worse DBS outcome. No significant changes in reward processing were observed following vALIC DBS in comparison to healthy controls or after active compared to sham stimulation. Instead, increased middle frontal gyrus responses following DBS to loss feedback was associated with better DBS outcome. These results suggest that DBS efficacy in TRD is related to individual differences in reward circuit functioning at baseline and to changes in middle frontal gyrus responses following DBS.