Apathy following deep brain stimulation in Parkinson's disease visualized by 7-Tesla MRI subthalamic network analysis

Background: Apathy is reported after subthalamic nucleus deep brain stimulation (STN DBS) and associated with a decreased quality of life in Parkinson's disease (PD) patients. Recent studies hypothesized that the location of active DBS contact point relative to the STN subdivisions (motor, associative and limbic) could be related to an increase of apathy. Methods: 22 PD-patients that underwent STN DBS between January 2019 and February 2020 were divided in an apathy and non-apathy group using the change in the Starkstein Apathy Scale (SAS) after six months of DBS. For both groups the location of DBS electrodes was determined based on 7T MRI subthalamic network analysis, enabling visualization of the subdivisions and their projections relative to the active contact point. MDS-UPDRS III scores were included to evaluate DBS effect. Results: In six patients a post-DBS increase in apathy score was assessed, versus 16 non-apathy patients. Network analysis showed that active contacts in apathy patients were more often positioned in or close to the area within the STN with high density of surrounding projections to associative cortex areas than in non-apathy patients; 63% apathy versus 42% (P = 0.02). The density of surrounding motor projections was lower in the group with increased apathy (18%) than in the group without increased apathy (38%, P = 0.01). Motor UPDRS improvement for the apathy group was 39% and for the non-apathy group 58% (n.s.) Conclusion: This new approach in patient-specific subthalamic 7T MRI network analysis visualized an anatomical connectivity substrate for apathy in DBS, with active electrode contacts predominantly in the associative STN.