Toward connectomic brain stimulation

• Applicant: Professor Dr. Andreas Horn, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 410169619

In deep brain stimulation (DBS), a paradigm shift has happened from studying localized therapeutic effects (e.g. relationship between DBS electrode placement and clinical symptom improvement) toward analyzing the impact of DBS on distributed brain networks (relationship between brain connectivity of DBS electrodes with other brain areas and clinical outcome). In a recent study, we could demonstrate that the connectivity fingerprint of DBS electrodes may be used to accurately predict clinical outcome of Parkinson‘s Disease (PD) patients across cohorts that were operated in different DBS centers. Building upon these findings, in the future, DBS electrode connectivity may pave the way toward patient-specific DBS that is taylored to the connectivity profile of a specific patient. In this sense, if the approach is further validated and refined, brain connectivity may one day guide both surgical planning and postoperative DBS programming. As a first building block, the present proposal aims at i) deepening the knowledge and methodology needed to establish the concept of connectomic deep brain stimulation, ii) transferring the findings from PD to other diseases and finally, iii) translating the findings into clinical practice. In more detail, the proposal aims at demonstrating symptom specificity of connectivity maps, transferability of connectivity findings across treatment sites and applicability in single patients. A second reason that makes the concept of connectomic DBS attractive is its potential to inform noninvasive treatment targets. Namely, optimal connectivity profiles of DBS electrodes to treat a specific disease embody cortical maps that could directly inform noninvasive targets for transcranial magnetic stimulation (TMS) or multifocal transcranial direct current stimulation (tDCS). In fact, we were able to prospectively validate this concept in a recent trial for TMS in Depression. As a second building block, the present proposal aims at building upon these results and to transfer the approach toward noninvasively treating PD. If successful, the proposed research program will have a strong impact on the field of neuromodulation and include first steps toward translating the concept into clinical practice.

• DFG Programme: Independent Junior Research Groups