Subthalamic nucleus deep brain stimulation in Meige syndrome: mapping the optimal stimulation sites and network targets

OBJECTIVE: The aim of this study was to identify the optimal stimulation sites for subthalamic nucleus (STN) deep brain stimulation (DBS) in treating Meige syndrome using long-term follow-up data from a large sample cohort, evaluate the whole-brain functional connectivity patterns associated with favorable treatment responses, and validate these findings in an independent cohort. METHODS: The authors retrospectively analyzed long-term outcomes in 65 patients with Meige syndrome who underwent bilateral STN-DBS in two centers. The local stimulation effects within the STN and the distributed functional connectivity associated with motor improvement were investigated using advanced imaging and modeling tools, including the Lead-Group Toolbox, DBS Sweet Spot Mapping Explorers, and DBS Network Mapping Explorers. To ensure the model's reliability and generalizability, both internal validation through multiple cross-validation strategies and external validation using independent cohorts were conducted. RESULTS: STN-DBS yielded significant and sustained motor improvements in both cohorts, with mean Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score reductions of 63% in the training cohort (n = 50) and 56% in the validation cohort (n = 15) (p < 0.001). At the local level, the optimal stimulation sites were consistently located in the dorsolateral sensorimotor subregion of the STN, extending bilaterally toward the associative subregion and centered at MNI coordinates x = ±12, y = -13, z = -6. At the network level, favorable outcomes were primarily associated with positive functional connectivity to the cerebellum and negative connectivity to the somatosensory cortex. Both the sweet spot and connectivity models developed using the training cohort showed significant correlations with clinical outcomes in the independent validation cohort (R = 0.59, p = 0.020; R = 0.74, p = 0.002, respectively) and remained robust across different cross-validation strategies. CONCLUSIONS: The optimal therapeutic efficacy of STN-DBS for Meige syndrome depends on precise targeting within the dorsolateral STN and modulation of a distributed functional network involving the cerebellum and sensorimotor cortex. These findings may aid in developing personalized targeting strategies and adaptive programming paradigms, ultimately improving the therapeutic efficacy of DBS in this challenging disorder.