Nucleus accumbens deep brain stimulation for major depressive disorder

• The Targets of Deep Brain Stimulation in the Treatment of Treatment-Resistant Depression: A Review
• Single-target Deep Brain Stimulation of the nucleus accumbens-anterior limb of the internal capsule for concurrent treatment of Tourette Syndrome, Obsessive-Compulsive Disorder, and Major Depressive Disorder: A case study
• Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression
• Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression
• NAc-DBS corrects depression-like behaviors in CUMS mouse model via disinhibition of DA neurons in the VTA
• Active versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial
• Parameter-based analysis of clinical efficacy of combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression
• The ventral capsule and ventral striatum-Stereotactic targets for the management of treatment-resistant depression. A systematic literature review

Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased pAMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD ¹⁾

DBS seems to be a promising technique in resistant major depressive disorder MDD treatment ²⁾.