Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson’s disease (PD) has been associated with neuropsychiatric symptoms such as impulsivity and hypomania. These symptoms can necessitate psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken.
Methods: We examined 64 patients undertaking subthalamic DBS. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with clinically-significant emergent symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms.
Results: Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency test at 6-weeks and 13-weeks postoperatively. Subthalamic voxels associated with inhibitory errors were identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion and stimulation within the right associative subregion. At 13-weeks, clinically-significant symptoms were associated with the distance to the right and left associative subregions and stimulation within the right associative subregion. Subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. A classifier trained on these data predicted clinically-significant symptoms with an accuracy of 79%.
Conclusions: These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention, improving safety and tolerability.
Patient Care: Predict and prevent neuropsychiatric complications of subthalamic deep brain stimulation for Parkinson's disease.
Learning Objectives: Improve outcomes and reduce neuropsychiatric side-effects for persons with Parkinson's disease undertaking subthalamic deep brain stimulation.