P 18 Can connectivity link the effects of STN and VIM DBS across tremor-related diseases? A multi-cohort functional connectivity study

Abstract

Introduction: Tremor is defined as an involuntary, rhythmic oscillatory movement of a body part and represents one of the most common symptoms in movement disorders, existing across several diseases. Particularly, in advanced states of tremor-related diseases such as Parkinson’s disease (PD) and Essential tremor syndrome (ET), response to pharmacotherapy can be insufficient and side effects may occur. In recent decades, deep brain stimulation (DBS) of the ventro-intermediolateral nucleus (VIM) and the subthalamic nucleus (STN) has become an established treatment option that can lead to alleviation of tremor in ET and PD patients, respectively. It is known that correlates of structural connections, such as the dentato-rubro-thalamic tract, are beneficial in tremor syndromes during stimulation, whereas information on the exact functional networks associated with optimal tremor response is lacking. However, analysis of connectivity profiles has been shown to reveal associations between electrode localization and clinical improvement in both PD and ET patients with DBS, and is therefore a powerful tool for investigating further disease- and possibly symptom-specific networks. Objective: Our aim is to investigate functional cerebral tremor networks of a multi-center cohort of PD- and ET-patients considering different surgical DBS targets. Patients & Methods: A total of 113 PD patients from DBS centers Berlin, Würzburg and Amsterdam with STN DBS were included in our study. In the STN DBS cohort, patients without tremor at baseline (< 3 points on UPDRS) were excluded from further analysis. The ET cohort consisted of 36 ET patients with VIM DBS. DBS electrodes in all patients were localized using Lead-DBS software. Seeding from voxels contained in the volume of activated tissue, a functional connectivity profile was calculated followed by voxel-wise correlation of clinical improvements with connectivity values. Across patients, connectivity values were correlated with tremor improvements, resulting in an “R-map” model of connectivity profile associated with maximal tremor response. R-maps of both cohorts were compared and combined to a map showing the agreement between R-maps of both cohorts. Results: Both R-maps showed positive associations to M1 and negative correlations to cerebellar regions, reflected in the agreement map. Connectivity to the agreement map was associated with tremor improvement, independently from underlying disease and target. Conclusion: Similar connectivity profiles were associated with optimal improvement of tremor following both STN-DBS for PD and VIM-DBS for ET. While recent connectivity network analyses for the entire UPDRS-III in PD patients revealed differences from networks in ET patients, our results suggest that a symptom-specific, common network for tremor exists across both ET and PD patients and that the network can be modulated at different target nodes.