LAUSR

BACKGROUND Tractography based on diffusion-weighted magnetic resonance imaging (DWI) models the structural connectivity of the human brain. Deep brain stimulation (DBS) targeting the subthalamic nucleus is an effective treatment for advanced Parkinson's disease but may induce adverse effects. This study investigated the relationship between structural connectivity patterns of DBS electrodes and stimulation-induced side effects. METHODS Twenty-one patients with Parkinson's disease treated with bilateral subthalamic DBS were examined. Overall, 168 electrode contacts were categorized as inducing or non-inducing depending on their capability for inducing side effects like motor effects, paresthesia, dysarthria, oculomotor effects, hyperkinesia, and other complications as assessed during the initial programming session. Furthermore, the connectivity of each contact with target regions was evaluated by probabilistic tractography based on DWI. Finally, stimulation sites and structural connectivity patterns of inducing and non-inducing contacts were compared. RESULTS Inducing contacts differed across the various side effects and from those mitigating Parkinson's symptoms. Although contacts showed a largely overlapping spatial distribution within the sub-thalamic region, they could be distinguished by their connectivity patterns. In particular, inducing contacts were more likely connected with supplementary motor areas (hyperkinesia, dysarthria), frontal cortex (oculomotor), fibers of the internal capsule (paresthesia), and the basal ganglia-thalamo-cortical circuitry (dysarthria). DISCUSSION Side effects induced by DBS seem to be associated with distinct connectivity patterns. Cerebellar connections are hardly associated with side effects, although they seem relevant for mitigating motor symptoms in Parkinson's disease. A symptom-specific, connectivity-based approach for target planning in DBS may enhance treatment outcomes and reduce adverse effects.