Structural connectivity of low-frequency subthalamic stimulation for improving stride length in Parkinson's disease.

ABSTRACT

BACKGROUND: A reduction in stride length is considered a key characteristic of gait kinematics in Parkinson's disease (PD) and has been identified as a predictor of falls. Although low-frequency stimulation (LFS) has been suggested as a method to improve gait characteristics, the underlying structural network is not well understood. OBJECTIVE: This study aims to investigate the structural correlates of changes in stride length during LFS (85 Hz). METHODS: Objective gait performance was retrospectively evaluated in 19 PD patients who underwent deep brain stimulation (DBS) at 85 Hz and 130 Hz. Individual DBS contacts and volumes of activated tissue (VAT) were computed using preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans. Structural connectivity profiles to predetermined cortical and mesencephalic areas were estimated using a normative connectome. RESULTS: LFS led to a significant improvement in stride length compared to 130 Hz stimulation. The intersection between VAT and the associative subregion of the subthalamic nucleus (STN) was associated with an improvement in stride length and had structural connections to the supplementary motor area, prefrontal cortex, and pedunculopontine nucleus. Conversely, we found that a lack of improvement was linked to stimulation volumes connected to cortico-diencephalic fibers bypassing the STN dorsolaterally. The robustness of the connectivity model was verified through leave-one-patient-out, 5-, and 10-fold cross cross-validation paradigms. CONCLUSION: These findings offer new insights into the structural connectivity that underlies gait changes following LFS. Targeting the non-motor subregion of the STN with LFS on an individual level may present a potential therapeutic approach for PD patients with gait disorders.