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Background: Pain is highly prevalent in Parkinson's disease and is associated with significant reduction in health-related quality of life. Subthalamic deep brain stimulation can produce significant pain relief in a subset of patients after surgery. However, the mechanism by which deep brain stimulation modulates sensory function in Parkinson's disease remains uncertain.Objective: To describe the motor and pain outcomes of deep brain stimulation applied to a series of patients with Parkinson's disease and to determine whether the structural connectivity between the volume of tissue activated and different regions of the brain was associated with the changes of these outcomes after surgery.Methods: Data from a long-term prospective cohort of 32 Parkinson's disease patients with subthalamic stimulation were combined with available human connectome to identify connections consistently associated with clinical improvement (Unified Parkinson Disease Rating Scale), pain intensity, and experimental cold pain threshold after surgery. Results:The connectivity between the volume of tissue activated and a distributed network of sensory brain regions (prefrontal, insular and cingulate cortex, and postcentral gyrus) was inversely correlated with pain intensity improvement and reduced sensitivity to cold pain after surgery (p < 0.01). The connectivity strength with the supplementary motor area positively correlated with motor and pain threshold improvement (p < 0.05).Conclusions: These data suggest that the pattern of the connectivity between the region stimulated and specific brain cortical area might be responsible, in part, for the successful control of motor and pain symptoms by subthalamic deep brain stimulation in Parkinson's disease.

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Fig. 1. Bilateral deep brain stimulation (DBS) of the dentate nucleus and relation with dentatorubrothalamic tracts (DRTT). Three-dimensional depictions of electrode placement in the dentate nucleus and its relations to the dentate-rubro-thalamic tract (DRTT). Fig. 1A and B result from a co-registration of pre-operative MRI with patient-specific deterministic tractography and post-operative CT (Elements Software, Brainlab AG, Germany). Fig. 1C originates from a co-registration of pre-operative MRI and post-operative CT, however normalized to the MNI space and comparing electrode position with a normalized DRTT projection (LEAD DBS Software, Horn & Kuehn, Germany).