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Brain. 2019 Nov 1;142(11):3592-3604. doi: 10.1093/brain/awz285.

Non-motor outcomes depend on location of neurostimulation in Parkinson's disease.

Author information

University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.
Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany.
Department of Neurology and Neurosurgery, Salford Royal Foundation Thrust, Greater Manchester, UK.
National Parkinson Foundation Centre of Excellence, King's College Hospital, London, UK.
Department of Neurology, University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany.
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
Division of Functional Neurosurgery of Institute of Psychiatry, Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain.
Department of Neuroscience, University of Padua, Padua, Italy.
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne, Germany.
The Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.


Deep brain stimulation of the subthalamic nucleus is an effective and established therapy for patients with advanced Parkinson's disease improving quality of life, motor symptoms and non-motor symptoms. However, there is a considerable degree of interindividual variability for these outcomes, likely due to variability in electrode placement and stimulation settings. Here, we present probabilistic mapping data from a prospective, open-label, multicentre, international study to investigate the influence of the location of subthalamic nucleus deep brain stimulation on non-motor symptoms in patients with Parkinson's disease. A total of 91 Parkinson's disease patients undergoing bilateral deep brain stimulation of the subthalamic nucleus were included, and we investigated NMSScale, NMSQuestionnaire, Scales for Outcomes in Parkinson's disease-motor examination, -activities of daily living, and -motor complications, and Parkinson's disease Questionnaire-8 preoperatively and at 6-month follow-up after surgery. Leads were localized in standard space using the Lead-DBS toolbox and individual volumes of tissue activated were calculated based on clinical stimulation settings. Probabilistic stimulation maps and non-parametric permutation statistics were applied to identify voxels with significant above or below average improvement for each scale and analysed using the DISTAL atlas. All outcomes improved significantly at follow-up. Significant spatial distribution patterns of neurostimulation were observed for NMSScale total score and its mood/apathy and attention/memory domains. For both domains, voxels associated with below average improvement were mainly located dorsal to the subthalamic nucleus. In contrast, above average improvement for mood/apathy was observed in the ventral border region of the subthalamic nucleus and in its sensorimotor subregion and for attention/memory in the associative subregion. A trend was observed for NMSScale sleep domain showing voxels with above average improvement located ventral to the subthalamic nucleus. Our study provides evidence that the interindividual variability of mood/apathy, attention/memory, and sleep outcomes after subthalamic nucleus deep brain stimulation depends on the location of neurostimulation. This study highlights the importance of holistic assessments of motor and non-motor aspects of Parkinson's disease to tailor surgical targeting and stimulation parameter settings to patients' personal profiles.


deep brain stimulation; non-motor symptoms; subthalamic nucleus; volume of activated tissue; volume of tissue activated


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