Flexible and Stable Cycle-by-Cycle Phase-Locked Deep Brain Stimulation System Targeting Brain Oscillations in the Management of Movement Disorders
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Background
Phase-locked neuromodulation aligns electrical or magnetic stimulation with the brain’s natural rhythms, showing promising potential to enhance therapeutic outcomes by more precisely modulating specific neural oscillations. However, stimulation-induced artifacts critically compromise real-time phase estimation accuracy. Existing approaches either suspend phase-tracking following stimulation or employ dedicated hardware systems yet introduce estimation instability through temporal gaps and signal distortion.
Objective
We develop and evaluate a flexible and stable phase-locked deep brain stimulation (PLDBS) system capable of delivering cycle-by-cycle phase-aligned stimulation based on brain oscillations, with an additional focus on its potential for modulating movement.
Methods
The PLDBS system was implemented using portable CE-marked devices and a computer-in-the-loop framework. Simulations and clinical experiments were performed targeting distinct phases of neural oscillations. The simulation framework evaluated the real-time performance of different phase-tracking methodologies considering artifacts, ultimately establishing a Kalman filter-based artifact removal system integrated with non-resonant oscillators for instantaneous phase estimation, thereby defining the final cycle-by-cycle PLDBS architecture. We then evaluated the performance of the pipeline for PLDBS in human patients targeting cortical alpha and subthalamic nucleus (STN) beta rhythms.
Results
Our system achieved over 90% accuracy in delivering stimulation within a 90°and 45°window centered around the target phase for STN beta (proximal recording) and cortical alpha rhythms (distal recording), respectively. Stimulation delivered at different STN beta phases led to a significant difference in evoked potentials in STN local field potentials in 3 out of 4 participants. However, such an effect was not found in cortical alpha in any 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 devices and a computer-in-the-loop. Using this pipeline, we showed that PLDBS at different STN beta phases differentially modulates the evoked action potentials in the STN and motor behavior used to quantify bradykinesia, paving the way for further studies and clinical trials for PLDBS.
