Non-motor effects of subthalamic nucleus stimulation in Parkinson\'s patients

Introduction: The existing white matter connectivity analyses of the subthalamic region have mainly included the motor effects of deep brain stimulation. We investigate white matter connectivity associated with the stimulation-induced non-motor acute clinical effects in three domains: mood changes, dizziness and sweating. Methods: Using whole brain probabilistic tractography and seeding from the volumes of tissue activation, connectivity maps were generated and statistically compared across patients. The cortical voxels associated with each non-motor domain were compared with stimulation-induced motor improvements in a multivariate model. The resulting voxels maps were thresholded for false discovery (FDR q<0.05) and clustered using a multimodal atlas. To understand the role of local pathways in the subthalamic region, a group level parcellation was performed for each non-motor domain. Results: The non-motor effects are rarely observed during stimulation titration: from 1100 acute clinical effects, mood change was observed in 14, dizziness in 23, and sweating in 20. Distinct cortical clusters were associated with each domain, notably mood change was associated with voxels in salience network and dizziness with voxels in visual association cortex. The subthalamic parcellation yielded a medio-lateral gradient with motor parcel being lateral and the non-motor parcels being medial. We also observed an antero-posterior organization in the medial non-motor clusters with mood changes (anterior), dizziness and sweating (posterior). Conclusion: We interpret these findings based on the literature and foresee these to be useful for shaping the electrical field with the imminent use of steerable DBS electrodes.