Abstract
Closed-loop strategies for deep brain stimulation (DBS) are paving the way for improving the efficacy of existing neuromodulation therapies across neurological disorders. Unlike continuous DBS, closed-loop DBS approaches (cl-DBS) optimize the delivery of stimulation in the temporal domain. However, clinical and neurophysiological manifestations exhibit highly diverse temporal properties and evolve over multiple time-constants. Moreover, throughout the day, patients are engaged in different activities such as walking, talking, or sleeping that may require specific therapeutic adjustments. This broad range of temporal properties, along with inter-dependencies affecting parallel manifestations, need to be integrated in the development of therapies to achieve a sustained, optimized control of multiple symptoms over time. This requires an extended view on future cl-DBS design. Here we propose a conceptual framework to guide the development of multi-objective therapies embedding parallel control loops. Its modular organization allows to optimize the personalization of cl-DBS therapies to heterogeneous patient profiles. We provide an overview of clinical states and symptoms, as well as putative electrophysiological biomarkers that may be integrated within this structure. This integrative framework may guide future developments and become an integral part of next-generation precision medicine instruments.
Highlights
Specialty section: This article was submitted to Neural Technology, a section of the journal Frontiers in Neuroscience
Throughout the day, patients are engaged in different activities such as walking, talking, or sleeping that may require specific therapeutic adjustments. This broad range of temporal properties, along with inter-dependencies affecting parallel manifestations, need to be integrated in the development of therapies to achieve a sustained, optimized control of multiple symptoms over time. This requires an extended view on future cl-deep brain stimulation (DBS) design
Its modular organization allows to optimize the personalization of closed-loop DBS approaches (cl-DBS) therapies to heterogeneous patient profiles
Summary
Motor and non-motor symptoms exhibit highly diverse temporal properties They emerge at different timepoints, progress at various speeds over the course of the disease, and diurnally fluctuate in intensity with according to their own variable time-constants. Tremor oscillations (∼5 Hz, 5 oscillations per second) stand in contrast to slow-changing states such as a dopaminergic wearing off episodes, which affect the condition of patients in the range of hours. Both states can be temporally related, as the likelihood of tremor episodes in PD may increase during wearing OFF dopaminergic states. Throughout the day, patients are engaged in different physiological states such as walking, talking, or sleeping, which may continuously or intermittently be affect by disease-specific symptoms
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