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TRR 295:  Retuning dynamic motor network disorders using neuromodulation

Subject Area Medicine
Computer Science, Systems and Electrical Engineering
Physics
Term since 2020
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 424778381
 
Reduced mobility is a leading source of disability worldwide. Among all neurological disorders resulting in motor impairment Parkinson's disease is the fastest growing in prevalence, disability and deaths according to the Global Burden of Disease study. Neuromodulation has demonstrated to restore motor deficits in movement disorder patients as best exemplified by deep brain stimulation (DBS) in Parkinson’s disease (PD). The starting point for our initiative is the recent development that many brain disorders have been reinterpreted from a network perspective, where motor and non-motor symptoms can be characterized as dysfunctions in task-specific brain circuits. The TRR 295 was launched in July 2020 with the overarching hypothesis that neuromodulation therapies allow abnormal brain signaling to be retuned and motor function to be restored by either eliminating pathological network activity, enhancing normal interareal communication, or activating compensatory circuits. During the first funding period, we developed first predictive algorithms for optimizing DBS settings in PD and dystonia based on imaging and connectivity measures, which have been validated in clinical trials and brought the TRR 295 to the forefront of digital expert systems (‘Stimfit’, ‘DIPS’). We further established important methodological innovations for simultaneous cortico-subcortical human recordings together with advancement in signal analysis of multivariate data and computational modeling that enabled us to identify symptom-specific biomarker and to develop unbiased quantification of abnormal movements. The parallel characterization of rodent models of disease that extend over the entire disease trajectory provide a platform for validating dynamic interventions (e.g., patterned or adaptive stimulation) in preclinical models and pilot clinical trials. Our long-term aim is to develop individualized, symptom-specific, and brain state-dependent, adaptive neuromodulation of motor and non-motor disorders based on a better understanding of the neurobiological basis of abnormal network communication in brain disorders. In the planned second funding period, we will expand our research focus towards the dynamic aspects of network dysfunction and plasticity mechanisms, enabling us to define the optimal temporal and contextual framework for targeted interventions. Specifically, we aim at (i) personalized neuromodulation treatment, based on state-dependent and symptom-specific interventions in motor and non-motor networks; (ii) the modification of disease trajectories through novel neuromodulation strategies targeted at rebalancing the compensatory and maladaptive network mechanisms. To this end, we have assembled a multidisciplinary team of top researchers – from engineering, computational sciences, signal theory, and basic and clinical neurosciences – that will facilitate therapy development from bench to bedside and vice versa.
DFG Programme CRC/Transregios
International Connection Israel

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Applicant Institution shared FU Berlin and HU Berlin through:
Charité - Universitätsmedizin Berlin
Participating Institution Tel- Aviv Sourasky Medical Center
 
 

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