Neurobiology of disease · 2026
Pallidal and subthalamic deep brain stimulation for cranio-cervical dystonia: Optimal stimulation sites and a convergent pathway.
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Fan Houyou, Hua Tiantian, Xu Yichen, Guo Zijian, Elias Gavin J B, Yin Zixiao, Jiang Yin, Xie Hutao, Hu Tianqi, Xue Tao, Zhao Zehua, Hu Tianxue, Liu Huanguang, Yang Anchao, Boutet Alexandre, Lozano Andres M, Li Ningfei, Horn Andreas, Germann Jurgen, Bai Yutong, Zhang Jianguo
Аннотация
BACKGROUND: Though deep brain stimulation (DBS) has emerged as a promising treatment for idiopathic cranio-cervical dystonia (iCCD), the best location at which to stimulate remains unclear at a granular level. This study aimed to identify optimal sites and related white matter pathways of globus pallidus internus (GPi) and subthalamic nucleus (STN) for DBS therapy.
METHODS: We analyzed a total of 70 iCCD patients treated with bilateral DBS, targeting the STN (n = 40) or GPi (n = 30). A retrospective cohort (n = 48) was utilized for training, while a prospective cohort (n = 22) was used for out-of-sample validation. We identified optimal stimulation sites, validating their spatial specificity and reproducibility. Target-specific and convergent "sweet tracts" for STN and GPi-DBS were identified based on a human axonal pathway model (the Basal Ganglia Pathway Atlas).
RESULTS: Optimal stimulation in both GPi and STN targeted distinct subregions mapped to cranio-cervical motor control-specifically, the posterior ventrolateral GPi and dorsolateral STN. Therapeutic "sweet tracts" engaged craniocervical- and dystonia-specific fiber pathways within the basal ganglia-thalamo-cortical loop, including the GPi-specific lenticular fasciculus, the STN-specific hyperdirect pathway and corticospinal tract, and the convergent posterior subthalamo-pallidal connections pathway. This convergent pathway was independently validated using a streamline-level analysis.
CONCLUSION: Our work provides a network-based explanation for the comparable efficacy of GPi and STN stimulation, suggesting that therapeutic benefit is driven by modulating specific pathways rather than the nucleus alone. This provides a new framework for refining and personalizing therapy.
METHODS: We analyzed a total of 70 iCCD patients treated with bilateral DBS, targeting the STN (n = 40) or GPi (n = 30). A retrospective cohort (n = 48) was utilized for training, while a prospective cohort (n = 22) was used for out-of-sample validation. We identified optimal stimulation sites, validating their spatial specificity and reproducibility. Target-specific and convergent "sweet tracts" for STN and GPi-DBS were identified based on a human axonal pathway model (the Basal Ganglia Pathway Atlas).
RESULTS: Optimal stimulation in both GPi and STN targeted distinct subregions mapped to cranio-cervical motor control-specifically, the posterior ventrolateral GPi and dorsolateral STN. Therapeutic "sweet tracts" engaged craniocervical- and dystonia-specific fiber pathways within the basal ganglia-thalamo-cortical loop, including the GPi-specific lenticular fasciculus, the STN-specific hyperdirect pathway and corticospinal tract, and the convergent posterior subthalamo-pallidal connections pathway. This convergent pathway was independently validated using a streamline-level analysis.
CONCLUSION: Our work provides a network-based explanation for the comparable efficacy of GPi and STN stimulation, suggesting that therapeutic benefit is driven by modulating specific pathways rather than the nucleus alone. This provides a new framework for refining and personalizing therapy.