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PLoS One. 2017 Mar 8;12(3):e0173363. doi: 10.1371/journal.pone.0173363. eCollection 2017.

Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation.

Author information

Institute of Neuroscience and Medicine - Neuromodulation, Jülich Research Center, Jülich, Germany.
Institute of Physics and Astronomy, University of Potsdam, Potsdam-Golm, Germany.
Department of Neurosurgery, Stanford University, Stanford, California, United States of America.
Department of Neuromodulation, University of Cologne, Cologne, Germany.


High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson's disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS.

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