Patient-Specific Anisotropic Volume of Tissue Activated with the Lead-DBS Toolbox.

Deep brain stimulation is an effective neurosurgical intervention for movement disorders such as Parkinson's disease. Despite its success, the underlying mechanisms are still debated. One tool to better understand them is the Volume of Tissue Activated (VTA), that estimates the region activated by electrical stimulation. Different estimation approaches exist, these typically assume isotropic tissue properties and modelling of anisotropy is often lacking.The present work was aimed at developing and testing a method for patient-specific VTA estimation that incorporated an anisotropic conduction model. Our method was implemented within the open-source toolbox Lead-DBS and is accessible to the public.The present method was further tested with two patient cases and compared to a standard Lead-DBS pipeline for VTA estimation. This showed encouraging similarities in one test scenario and expected differences in another test scenario. Further validation with a wider cohort is warranted.

Structure-function relationship of the posterior subthalamic area with directional deep brain stimulation for essential tremor.

Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area. We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4-6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects. Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level. Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.