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Pallidal and subthalamic stimulations modulate inter-hemispheric interaction and asymmetry in Parkinson’s disease

Molecular Psychiatry (2026)Cite this article

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Abstract

Substantial asymmetries of motor dysfunction are evident in patients with Parkinson’s disease (PD), the mechanisms of which remain largely unexplored. This study investigated how deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) and subthalamic nucleus (STN) modulates characteristics of hemispheric lateralization in PD patients, with particular emphasis on motor asymmetries and hemispheric integration (via homotopic functional connectivity) and segregation (via hemispheric asymmetry in connectivity). Resting-state functional magnetic resonance imaging (fMRI) and Unified Parkinson’s Disease Rating Scale (UPDRS) III scores were analyzed from 55 PD patients who underwent either bilateral GPi- or STN-DBS. Both targets produced significant improvements in motor function. Notably, stimulation effects on motor asymmetry depend on patients’ baseline asymmetry direction (DBS OFF): STN-DBS consistently reduced asymmetry in the leftward-asymmetry patients, whereas GPi-DBS has stronger effects in rightward patients. In both cases, stimulation led to a more symmetric pattern. Beyond motor outcomes, motor gains were associated with changes in homotopic connectivity in the lateral occipital region, overlapping the extrastriate body area, suggesting a compensatory role of visual networks. These findings highlight the contribution of the visual networks to motor improvement and reveal target-dependent effects of DBS on both motor asymmetry and non-motor cognitive domains.

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Fig. 1: Study overview and methodological framework.
Fig. 2: DBS-related modulation of the two functional connectivity metrics indexing hemispheric organization.
Fig. 3: Motor correlates of the DBS-related changes in the brain.
Fig. 4: Functional decoding results of the DBS-related changes in the functional connectome metrics.

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Data availability

The data supporting the findings of this study are provided in the Supplementary Materials. Additional raw data are available from the corresponding author upon reasonable request.

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Acknowledgements

Xiang-Zhen Kong was supported by Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project (2025ZD0218801; 2021ZD0200409), National Natural Science Foundation of China (32171031; 32571219), Fundamental Research Funds for the Central Universities (226-2025-00144), and Information Technology Center of Zhejiang University. Chencheng Zhang was supported by National Natural Science Foundation of China (82101547; 82471495). Yi Pu was supported by National Natural Science Foundation of China (32400882).

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  1. These authors contributed equally: Siyuan Mei, Naying He.

Authors and Affiliations

  1. Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China

    Siyuan Mei & Xiang-Zhen Kong

  2. The State Key Lab of Brain-Machine Intelligence, Zhejiang University, Hangzhou, China

    Siyuan Mei & Xiang-Zhen Kong

  3. Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Naying He & Fuhua Yan

  4. Clinical Neuroscience Center, RuiJin-Mihoyo Laboratory, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Weibin He, Junyi Yan & Chencheng Zhang

  5. School of Electrical and Information Engineering, Tianjin University, Tianjin, China

    Chunguang Chu

  6. Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Zhitong Zeng & Dianyou Li

  7. Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China

    Yi Pu

  8. Shanghai Research Center for Brain Science and Brain-Inspired Technology, Shanghai, China

    Chencheng Zhang

  9. Zhejiang Key Laboratory of Neurocognitive Development and Mental Health, Zhejiang University, Hangzhou, China

    Xiang-Zhen Kong

  10. Department of Psychiatry of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Xiang-Zhen Kong

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Contributions

SM: study conception and design, data preparation, analysis, visualization, preparing the first draft and editing; NH: data collection, study conception and design, manuscript editing; WH, JY, CC, ZZ, YF, DL: data collection and manuscript editing; YP: manuscript editing; CZ: data collection, study conception and design, manuscript editing; XK: study conception and design, data preparation, analysis, visualization, preparing the first draft and editing.

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Mei, S., He, N., He, W. et al. Pallidal and subthalamic stimulations modulate inter-hemispheric interaction and asymmetry in Parkinson’s disease. Mol Psychiatry (2026). https://doi.org/10.1038/s41380-026-03557-9

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