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<p>Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson’s disease (PD), but how it modulates whole-brain dynamics to drive therapeutic effects remains unclear. We hypothesized that STN-DBS restores signatures of cortical metastability—a dynamic balance between integration and segregation of neural networks—critical for adaptive behavior. Using a novel Weighted Eigenvector Dynamics Analysis (WEiDA) on resting-state fMRI data from PD patients, we identified four recurring probabilistic metastable substates (PMS). PD patients exhibited aberrantly low occupancy of a state characterized by decoupling between visual (VN) and somatomotor/ventral attention (SMN/VAN) networks (State V-VA/SM), which normalized with DBS and correlated with motor improvement. This rebalancing was mediated by decreased local metastability and enhanced functional segregation between VN and SMN/VAN modules, linked to cholinergic gene expression (<i>CHRNA10</i>). Notably, analogous normalization of metastable dynamics and symptom relief emerged during noninvasive STN-targeted temporal interference stimulation (tTIS), indicating converged network-level mechanisms across neuromodulation modalities. Our findings highlight cortical metastability signatures as a potential substrate for DBS efficacy in PD, bridging invasive and noninvasive therapeutic strategies through dynamic brain state modulation.</p>

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Neuromodulation-induced normalization of cortical metastable dynamics signatures in Parkinson’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Chenfei Ye,
  • Chen Ran,
  • Yongxin Xu,
  • Chunguang Chu,
  • Chenhao Yang,
  • Chencheng Zhang,
  • Yu Liu,
  • Ting Ma

摘要

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson’s disease (PD), but how it modulates whole-brain dynamics to drive therapeutic effects remains unclear. We hypothesized that STN-DBS restores signatures of cortical metastability—a dynamic balance between integration and segregation of neural networks—critical for adaptive behavior. Using a novel Weighted Eigenvector Dynamics Analysis (WEiDA) on resting-state fMRI data from PD patients, we identified four recurring probabilistic metastable substates (PMS). PD patients exhibited aberrantly low occupancy of a state characterized by decoupling between visual (VN) and somatomotor/ventral attention (SMN/VAN) networks (State V-VA/SM), which normalized with DBS and correlated with motor improvement. This rebalancing was mediated by decreased local metastability and enhanced functional segregation between VN and SMN/VAN modules, linked to cholinergic gene expression (CHRNA10). Notably, analogous normalization of metastable dynamics and symptom relief emerged during noninvasive STN-targeted temporal interference stimulation (tTIS), indicating converged network-level mechanisms across neuromodulation modalities. Our findings highlight cortical metastability signatures as a potential substrate for DBS efficacy in PD, bridging invasive and noninvasive therapeutic strategies through dynamic brain state modulation.