Mechanisms of nucleus accumbens deep brain stimulation in treating mental disorders

Growing evidence supports the effectiveness of deep brain stimulation (DBS) in treating various psychiatric disorders. DBS has the potential to selectively stimulate specific subcortical brain areas thus providing high-frequency electric stimulation of these regions. The nucleus accumbens (NAc), a frequent DBS target, has shown promise in treating psychiatric conditions like depression, obsessive-compulsive disorder, and addiction. In this review, we provide an overview across studies investigating the effects of NAc DBS in humans and animals and discuss potential mechanisms underlying its clinical efficacy. We address the anatomical properties of NAc and discuss, in particular, the frequently reported differential effects of NAc shell and NAc core DBS. Moreover, by outlining the various NAc cell types, transmitter systems (i.e., predominantly GABAergic and dopaminergic systems) and anatomical pathways that have been shown to be relevant for NAc DBS stimulation effects, we aim to further elucidate the neurobiological determinants of NAc DBS efficacy. Finally, since treatment effects of NAc DBS are most probably also related to alterations in NAc connected circuits or networks, we review studies focusing on the investigation of NAc DBS network effects. By examining these various components that are assumed to be of relevance in the context of NAc DBS, this review will hopefully contribute to increasing our knowledge about the mechanisms underlying NAc DBS and optimizing future selection of optimal DBS targets.