Deep brain stimulation: from mechanism to application

Deep brain stimulation (DBS) has emerged as a transformative neuromodulation therapy for a variety of neurological and psychiatric disorders, including Parkinson’s disease, epilepsy, and obsessive-compulsive disorder. Despite its widespread clinical use, the precise mechanisms underlying these therapeutic effects remain incompletely understood. This review provides a comprehensive examination of DBS, from its historical development and underlying mechanisms to its diverse clinical applications in 16 diseases. The historical context traces the evolution of DBS technology from early stereotactic techniques to contemporary advances that allow for more precise targeting and adaptive stimulation. Mechanistically, DBS influences neural activity through a combination of depolarization block, informational lesion, and network reconfiguration via induced neuroplasticity. Each mechanism may contribute uniquely to symptom mitigation and therapeutic outcome. The most advanced and widely studied clinical applications of DBS are alleviating motor symptoms in Parkinson’s disease, managing refractory epilepsy, and addressing treatment-resistant psychiatric conditions. While highlighting these three major application conditions, we also map therapeutic interventions across a broader spectrum of emerging indications. The future of DBS lies in adaptive systems that optimize stimulation based on real-time neural feedback, as well as in expanding applications to other disorders and targets. Continued research and technological advancements are crucial for enhancing the efficacy, precision, and accessibility of DBS, thereby broadening its therapeutic potential.