A clinical grade neurostimulation implant for hierarchical control of physiological activity

作者：Moaad Benjaber, Mayela Zamora, Robert A. Toth, John E. Fleming, Kei Landin, Victoria S. Marks, Rachel A. Crockett, Jae-Wook Ryou, Alceste Deli, Alexander L. Green, Rory J. Piper, Martin Tisdall, Derk‐Jan Dijk, Nicholas D. Schiff, Andrew Sharott, Keith P. Purpura, Jonathan Baker, Joram J. van Rheede, Timothy J Denison · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.10.21.683630 · 被引用次数：1 · 研究领域：Pain Management and Treatment、Transcranial Magnetic Stimulation Studies、Vagus Nerve Stimulation Research

Abstract Bioelectronic implants for neurostimulation aim to steer disordered neurophysiological processes back towards a healthy state. However, physiology is subject to biological rhythms, including the circadian rhythm and the sleep-wake cycle. These predictable rhythms affect disease symptomatology, biomarkers used in closed-loop therapies, and a physiological system’s expected response to stimulation. Therefore, therapeutic devices should incorporate feedforward elements to align algorithm parameters with predictable changes in physiological state, as a parallel of physiological rheostatic control. Here we introduce the DyNeuMo-2c, the first clinical-grade implant capable of delivering closed-loop neurostimulation while flexibly changing its functional configuration according to time of day. The device can chronically measure brain activity and motion state to track potential biomarker patterns in natural, out-of-clinic settings, allowing identification and targeting of patient-specific chronotypes. The system implements a hierarchical control flow, with baseline therapy set by a circadian scheduler, and adaptive policies layered to take effect based on specific biomarkers indicating patient and disease state. Using a benchtop validation setup, we demonstrate that the system has the required capabilities for delivering time-contingent closed-loop therapy in two established clinical use cases: Parkinson’s disease and epilepsy. Next, we deploy the system in vivo to deliver ...