Flexible and stable cycle-by-cycle phase-locked deep brain stimulation system targeting brain oscillations in the management of movement disorders

作者：Xuanjun Guo, Alek Pogosyan, Jean Debarros, Shenghong He, Laura Wehmeyer, Fernando Rodriguez Plazas, Karen Wendt, Zixiao Yin, Ahmed Raslan, Thomas Hart, Francesca Morgante, Timothy Denison, Erlick Pereira, Keyoumars Ashkan, Shouyan Wang, Huiling Tan · 发表于：Brain stimulation · 年份：2025 · DOI：10.1016/j.brs.2025.09.002 · 被引用次数：4 · 研究领域：Neurological disorders and treatments、Neuroscience and Neural Engineering、Transcranial Magnetic Stimulation Studies

BACKGROUND: Precisely timed brain stimulation, such as phase-locked deep brain stimulation (PLDBS), offers a promising approach to modulating dysfunctional neural networks by enhancing or suppressing specific oscillations. However, its clinical application has been hindered by the lack of user-friendly systems and the challenge of real-time phase estimation amid stimulation artifacts. MATERIAL AND METHOD: In this work, we developed a clinically translatable PLDBS framework that enables real-time, cycle-by-cycle stimulation using standard amplifiers and a computer-in-the-loop system. Our approach integrates Kalman filter-based artifact suppression and non-resonant oscillators for accurate phase tracking. We tested this system in a small clinical trial (n=4) targeting subthalamic nucleus (STN) stimulation at specific phases of cortical alpha and STN beta rhythms in patients with movement disorders during acute lead externalization following deep brain stimulation surgery. RESULT: The system delivered stimulation with over 90% accuracy, within ±π/2 for STN beta and ±π/4 for cortical alpha. Stimulations delivered at different STN beta phases led to a significant difference in evoked potentials in STN local field potentials in all participants. STN beta-triggered stimulation showed potential phase-dependent modulation of finger-tapping velocity and amplitude in Parkinson's disease. CONCLUSION: This study presents a flexible and stable pipeline for precise PLDBS with CE-marked devi...