Bridging Neural Circuits and Therapy: Advances in Deep Brain Stimulation
Abstract:
Deep brain stimulation (DBS) is an effective treatment for multiple neurological disorders, including advanced Parkinson's disease (PD), through continuous high-frequency brain stimulation. While its clinical benefits are well documented, the underlying mechanisms remain poorly understood. Due to the anatomical and cellular heterogeneity of brain tissue, DBS can modulate diverse neuronal elements and circuits at and around the stimulation site, many of which may not directly contribute to therapeutic effects. Moreover, conventional DBS systems typically operate in open-loop mode, delivering fixed stimulation parameters regardless of patient state or neural activity. Identifying the specific circuits that mediate therapeutic benefits is therefore critical for refining target selection and developing next-generation treatment strategies. Optogenetics provides a powerful tool to overcome the nonselective nature of DBS by enabling cell-type specific modulation of neural populations. By integrating optogenetic interventions with electrophysiological recordings, computational modeling, and behavioral assays in preclinical models of PD, our work seeks to dissect the circuit-level mechanisms underlying DBS and systematically evaluate how modulation of defined neural pathways alleviates parkinsonian motor symptoms. In addition, I will introduce our recent efforts toward the development and preclinical evaluation of closed-loop DBS systems, which dynamically adjust stimulation in response to ongoing neural and behavioral states. Together, these approaches aim to advance both our mechanistic understanding of DBS and the design of more effective, adaptive neuromodulation therapies for PD.