Abstract
Deep brain stimulation (DBS) is a neuromodulatory therapy involving the implantation of electrodes into brain structures in order to help normalize brain activity in a variety of neurological disorders. The mechanisms of DBS operate at micro-, meso-, and macroscale levels to influence neuronal signaling, synaptic reorganization, and network-wide connectivity between brain regions. Recent advances in connectomics and sensing technologies have allowed for more precise and adaptive stimulation strategies, increasing the potential to target complex, heterogeneous neuropsychiatric conditions. DBS has already been well-explored as a treatment for obsessive-compulsive disorder. Emerging research has explored the use of DBS for other neuropsychiatric conditions as well, including autism spectrum disorder (ASD), treatment-refractory depression (TRD), and dementia associated with Alzheimer's disease (AD). DBS for ASD shows promise in reducing self-injurious behaviors and aggression by targeting the nucleus accumbens (NAc), amygdala, and posteromedial hypothalamus. In TRD, DBS to the subcallosal cingulate gyrus (SCG), medial forebrain bundle (MFB), and ventral capsule/ventral striatum (VC/VS) has demonstrated significant antidepressant effects. For dementia and AD, DBS targeting the fornix and nucleus basalis of Meynert (NBM) has shown promise in slowing cognitive decline. Despite the variety of targets, connectomic analyses reveal overlapping cortical-subcortical network dysfunctions across these disorders. These findings offer insight into shared neurobiological mechanisms of these disorders, as well as guide refinement of therapeutic targets for future study. Overall, DBS for neuropsychiatric conditions remains in its early stages, hindered by disorder heterogeneity and challenges in identifying optimal brain targets. Advances in functional neuroimaging, closed-loop stimulation, and machine learning-driven connectomic approaches can aid in target selection as well as better understanding the neuroanatomy and physiology underlying these complex conditions, which, in turn, lead to improved patient outcomes. Further research is necessary to establish standardized protocols and expand the therapeutic applications of DBS in neuropsychiatry.