Prof. Dr. med. Peter Fuhr

Deep brain stimulation (DBS) has become one of the most important neurostimulation therapies for movement disorders as Parkinson’s disease (PD) and essential tremor (ET). Despite the success of this therapy the underlying mechanism(s) of action and optimal implantation locations are still incompletely known, and the post-operative stimulation parameter programming procedure remains time consuming, especially when using segmented stimulation leads. Our multidisciplinary, international consortium collaborating partially for more than 15 years, has a long-lasting experience in DBS research concerning brain imaging, patient-specific electric field (EF) simulation, tractography, intraoperative physiological measurements and atlas generation. The project relies on these established methods and is directly linked to an ongoing cross disciplinary international DBS research.

The primary objective of the present exploratory project is to set-up and evaluate a workflow for an inverse analysis algorithm to predict chronic DBS parameters in patients suffering from ET and implanted in Zona incerta (ZI) or the nucleus ventrointermedius of the thalamus (Vim).

To reach this goal, four main Work Packages (WPs) are planned within the proposed project.

WP1: Patient-specific improvement and adverse effect maps will be set-up for new data from the clinical partners, based on patient-specific EF simulations for intraoperative stimulation tests before DBS lead implantation and chronic stimulation with the corresponding clinical effects.

WP2: Mono- and multi-centric ZI/Vim ET DBS atlases with therapeutic (sweet spots) and adverse effect areas will be generated from these individual maps and possibly as well a PD atlas for the subthalamic nucleus.

WP3: The atlases will be projected to new patients. An algorithm for stimulation parameter prediction will be developed based on the mono-centric atlas to determine position and necessary stimulation parameters: the corresponding EFs should cover therapeutically effective and avoid adverse effect regions from the atlas.

WP4: The proof of concept will be performed with patient cohorts from two further clinical centers and through a comparison between predicted and finally chosen chronic stimulation parameters and stimulated volumes.

The stimulation atlases developed with larger patient cohorts are expected to enable new knowledge about the optimal areas to stimulate and those to avoid and thus about the optimal target position in different movement disorders. The inverse analysis of the stimulation atlases should support clinicians in choosing the stimulation parameters. A successful outcome will result in the replacement of the trial-and-error principal of the programming sessions. This will reduce the number of medical visits and programming time, and in consequence increase the patient comfort. In the long term, this approach could be applied to the surgical planning procedure to propose the optimal implant position. In summary, the approach proposed will take the next step in patient management in going from “mental imagination” by the medical staff to “intuitive visualization” to further improve DBS therapy.