Article
An effective connectivity profile for reducing freezing of gait after subthalamic nucleus stimulation
Netzwerk-Konnektivität für die Verbesserung von Freezing of Gait nach tiefer Hirnstimulation des Nucleus subthalamicus
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Published: | May 25, 2022 |
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Objective: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson's disease (PD). While the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been proven in large randomized, controlled trials, its effect on FOG is still insufficiently understood. Moreover, there is uncertainty about pathways that need to be modulated to improve FOG. This retrospective analysis aimed to investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity to cortical and subcortical areas of the stimulated tissue predicts outcome.
Methods: 47 subjects with PD and preoperative FOG were investigated. Freezing prevalence and severity were assessed using the Freezing of Gait Questionnaire (FOG-Q) and Item 14 of the Unified Parkinson's Disease Rating Scale-II. We reconstructed electrode localisation and volume of tissues activated (VTAs) for each patient using the Lead-DBS software. By overlapping the patients individual VTAs with a publicly available model of basal-ganglia pathways we determined a stimulation-dependent connectivity profile for postoperative changes in FOG. Additionally, a ROI analysis of this connectivity profile to a priori defined mesencephalic locomotor regions was performed.
Results: FOG significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation sites for improving freezing of gait structurally connected to primary and supplementary motor areas, the dorsolateral prefrontal cortex and to the globus pallidus internus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibres crossing the pedunculopontine nucleus (PPN) and the substantia nigra (SN) correlated with postoperative improvement of FOG.
Conclusion: STN-DBS can alleviate FOG severity by modulating specific circuitries associated with cognitive and motor function. While no significant association with clinical and demographic characteristics could be found, this connectivity profile was predictive of postoperative changes in FOG.