Prospective evaluation of determining the most effective contact for tremor control in patients with deep brain stimulation based on individual tractography (TremTract Study)

• Applicant: Dr. Jan Niklas Petry-Schmelzer
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2022 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 502436811

Deep brain stimulation (DBS) is an established treatment for diseases associated with tremor. The most common diesases are Essential Tremor (ET) and idiopathic Parkinson’s Disease (IPS). For the treatment of ET, DBS leads are implanted in the Nucleus ventralis intermedius oft he thalamus (VIM), whereas the Nucleus subthalamicus is targeted in IPS.While stereotactic DBS surgery for tremor control is based on anatomical landmarks, there is a shift oft the pathophysiological understanding of DBS effects on tremor away from target-point specific effects towards network specific effects. Regarding tremor, there is evidence for the inolvement of cerebello-thalamo-cortical networks. One oft he most important neuroanatomical substrates of this network is the dentato-rubro-thalamic tract (DRTT). Previous studies by the applicant and others provide evidence that the achievable postoperative tremor control by DBS depends on the proximity of the active contact to the DRTT. To date, as per current clinical routine, the most effective contact is postoperatively determined by troublesome and time-intensive (approx. 3.5 hours) clinical testing. During this clinical testing effect and side-effect thresholds are determined in steps of 0.5 mA for each contact.The aim of the proposed study is to evaluate prospectively the hypothesis of a symptom specific tremor network across diseases. This gain of pathophysiological understanding will then be translated to clinical practice. To do so a highly standardized and automatized imaging-based pipeline, based on voxel-based calculation of the overlap between the spread of stimulation and the DRTT, will be prospectively evaluated.The applied techniques were already established during previous studies and the applicant has an outstanding expertise in clinical and imaging-based studies in the field of DBS. As the clinical testing has to be done by a trained physician, funding for a "Ärztliche/r wissenschaftliche/r Mitarbeterin/Mitarbeiter" for the anticipated duration of the study is requested.In case of a positive evaluation, the proposed study provides Class II evidence for an imaging-based approach to determine the most effective contact for tremor control. In the future this approach can lead to a reduction of patient burden, time and related costs in contrast to the current approach based on clinical testing.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Michael Barbe