Connectivity Predicts deep brain stimulation outcome in <scp>P</scp>arkinson disease

TLDR

The benefit of deep brain stimulation for Parkinson disease may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome remain unknown. The study aims to identify the structural and functional connectivity profile of effective subthalamic nucleus DBS and test its ability to predict clinical outcome. A training cohort of 51 patients was combined with publicly available human connectome data to determine connections reliably associated with motor improvement measured by the UPDRS. The resulting connectivity profile predicted response in an independent cohort of 44 patients with an average 15% error, with structural and functional connectivity serving as independent predictors, and similar accuracy was obtained using connectomes from normal subjects or matched controls, demonstrating that prediction does not require specialized imaging. Published in Annals of Neurology 2017;82:67–78.

Abstract

The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort.A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center.In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients.Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.