BACKGROUND: Parkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). OBJECTIVES: The aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. METHODS: Resting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. RESULTS: While all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. CONCLUSIONS: STN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

3rd Faculty of Medicine Charles University Prague Prague Czech Republic

Center for Magnetic Resonance Research University of Minnesota Minneapolis MN USA

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Radiology Na Homolce Hospital Prague Czech Republic

Department of Science and Research Prague College of Psychosocial Studies Prague Czech Republic

Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany

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Sweet spot for resting-state functional MRI effect of deep brain stimulation in dystonia lies in the lower pallidal area