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Abstract Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for both motor and non-motor symptoms in advanced Parkinson's disease (PD). Outcomes, however, can vary significantly among patients. Therefore, neuroimaging markers, such as neurite orientation dispersion and density imaging (NODDI), a biophysical model-based MRI technique, have been proposed to predict clinical outcomes and aid in preoperative counselling. In this prospective open-label study, we aimed to identify microstructural metrics associated with short-term motor outcomes following STN-DBS in PD. Thirty-five patients underwent diffusion-weighted MRI and comprehensive clinical assessments before surgery and at a six-month follow-up postoperatively. Using a whole-brain voxel-wise approach, we explored associations between microstructural metrics and motor outcomes, adjusting for multiple comparisons employing permutation-based methods. Intact microstructure within the bilateral putamen, bilateral insula, and left pallidum were associated with a higher reduction in postoperative motor symptom burden. Furthermore, preserved microstructure in pre- and postcentral gyrus and right precuneus were associated with increases in time with good mobility and no troublesome dyskinesia as well as decreases in time with poor mobility. These findings suggest that diffusion weighted MRI can be a valuable tool in preoperative counselling by identifying patients who are likely to experience above- or below-average motor responses.
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