Precision prediction of motor fluctuations in advanced Parkinson’s disease via multiregional neural sensing

Precise prediction of motor fluctuations is critical for the management of advanced Parkinson’s disease (PD). However, current single-region biomarkers show poor performance largely due to their mismatch with the network-level pathophysiology. This study presents a translatable multi-regional sensing framework for simultaneous recording from eight cortico-basal ganglia-thalamo-cortical (CBGT) circuit hubs in rodent models.

Application of a hierarchical loss-optimized multilayer perceptron (H-Lo-MLP) tailored for open-set clinical scenarios demonstrates that distributed CBGT oscillatory patterns substantially outperform single-region biomarkers. The H-Lo-MLP achieves nearly 90% prediction accuracy, far exceeding the ~50% of threshold-based approaches, with robust generalizability across disease progression and dopaminergic modulation. Systematic evaluation of all 255 region combinations identifies primary motor cortex (M1) and dorsal striatum as pivotal discriminative hubs and reveals a parsimonious four-region configuration that retains near-optimal predictive performance while minimizing surgical invasiveness.

Cross-species proof-of-concept in a single non-human primate recapitulates the conserved centrality of M1 and demonstrates the feasibility of simultaneous multi-region monitoring via a single linear electrode. These findings establish network-level sensing as a clinically viable paradigm for precise motor fluctuation prediction, overcoming limitations of constrained adaptive deep brain stimulation. By validating a surgically tractable, cross-species network-sensing approach, this work bridges the gap between circuit-level pathophysiology and clinical translation.

The authors acknowledge the support of the National Key Research and Development Program of China (Grant No. 2022YFC2405101) and the Lingang Laboratory (Grant No. The authors received no specific open access funding for this work. These authors contributed equally: Yu Chen, Shu Wang, Bo-Yu Wang.

Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing, China Yu Chen, Bo-Yu Wang, Bin Wang, Bing Wu, Xiao-Chang Hu, Lu-Bin Wang, Wen Xie, Yi-Zheng Wang & Chun-Kui Zhang Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China Correspondence to Jian-Guo Zhang, Yi-Zheng Wang or Chun-Kui Zhang. The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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