Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.