Functional Connectivity to the Cerebellum and Resting-State Networks Predict Earlier Improvement of Dystonia...

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment for dystonia. However, the time from device activation to clinical improvement is typically prolonged, variable, and unpredictable. While most patients improve gradually over months, some show significant benefit within weeks. The neuroanatomical and network-level mechanisms underlying early response remain unknown.

To investigate the structural and functional correlates of earlier symptom improvement in patients with isolated dystonia who responded to bilateral GPi-DBS.

This retrospective study enrolled 46 patients. Early responders were defined as achieving ≥25% reduction in Unified Dystonia Rating Scale (UDRS) scores within 3 months post-surgery. Preoperative magnetic resonance imaging (MRI) and postoperative computed tomography data were processed to localize electrodes, model volume of activated tissue, and calculate electric fields. Functional connectivity was assessed using normative resting-state functional MRI (fMRI) data, while structural connectivity was estimated using fiber filtering of a histology-based atlas.

A stimulation 'sweet spot' at the ventral border of the lateral GPi and medial globus pallidus externus (GPe) was associated with early improvement. Early response correlated with neuromodulation of GPe-subthalamic nucleus fibers and lenticular fasciculus. Stimulation sites connected to cerebellar cortex (lobules IX, crus I, crus II), default mode, and limbic networks were associated with earlier benefit.

These findings support a broader network model integrating cerebellum, limbic system, and basal ganglia in dystonia. Stimulation of cerebellar-connected circuits may accelerate improvement independent of classical somatomotor networks. Results highlight novel targets and mechanisms for improving DBS effectiveness, suggesting multitarget, network-informed strategies could enhance therapeutic outcomes. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.