Pallidal and subthalamic deep brain stimulation for cranio-cervical dystonia: Optimal stimulation sites and a...

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.

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).

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.

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.