Objective: To assess the scientific rationale and feasibility of a multimodal control paradigm for closed-loop deep brain stimulation (DBS) in Parkinson’s disease (PD) that combines slow systemic states (ex: behavior or underlying metabolic state) and fast central states (ex: neurophysiology).

Background: To assess the scientific rationale and feasibility of a multimodal control paradigm for closed-loop deep brain stimulation (DBS) in Parkinson’s disease (PD) that combines slow systemic states (ex: behavior or underlying metabolic state) and fast central states (ex: neurophysiology).

Method: We performed a structured literature review across PubMed, Scopus, and Web of Science (2014-2024). After screening over 300 records, 42 studies were selected for qualitative synthesis. The review was organized across five key categories: (1) biochemical Phenotyping in PD; (2) neurophysiological biomarkers for PD; (3) the systemic-central Link; (4) real-time sensing (internal and external data) and patient-reported outcomes; and (5) methodologies for multi-scale longitudinal studies. For each category, we identified: the state-of-the-art evidence supporting the multimodal concept; and critical knowledge gaps.

Results: The review confirmed that foundational components for a multimodal model are established but disconnected. Evidence supports a measurable slow systemic state (ex: glycemic variability, proteomic and hormonal factors) relevant to motor fluctuations and PD progression. Similarly, fast signals (ex: LFP beta power) are validated for state‑dependent control, though their long‑term, off‑therapy trajectories remain under‑characterized. The review highlights an opportunity to bridge the critical gap in the literature: the lack of studies that synchronously measure dynamic systemic changes with neurophysiology and behavioral signals (ex: kinematics) over meaningful timescales, specifically for PD.

Conclusion: Multimodal closed-Loop DBS that integrates slow systemic and fast central signals is conceptually sound and technically feasible. Our findings validate the need for a focused feasibility study designed to quantify this systemic-central link by providing the foundational evidence required to de-risk the development of truly personalized, biology-driven neuromodulation therapy for PD.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/assessing-the-feasibility-of-a-multimodal-control-model-for-deep-brain-stimulation-in-parkinsons-disease-a-structured-literature-review/