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

Our transregional collaborative research center (TRR) seeks to improve the understanding of the various symptoms of human movement disorders by elucidating symptom-specific neural activity and developing specific treatment strategies for network modulation in common and clinically-relevant neurological diseases. This includes Parkinsonism, dystonia, and tics, but also gait disorders related to abnormal patterning in cortical-subcortical circuits, including the cortex, basal ganglia, spinal cord, brainstem, or cerebellum. We hypothesize that neuromodulation is a promising tool that can modify network activity and restore motor function by eliminating pathological network activity, augmenting normal interareal communication, or activating compensatory circuits. Elucidating the neurobiological mechanisms of abnormal network communication in brain disorders will help us to advance neuromodulation therapy beyond the limitations of current neuromodulation therapies. Our long-term vision is to develop clinical neuromodulation approaches that are circuit-specific and suppress abnormal brain activity, but also restore or preserve normal function.In the first funding period of our TRR, we will focus on three main research areas: a) cell-to-cell interactions in motor disease networks; b) circuit modeling and imaging of motor disease networks; c) retuning of motor disease networks. Within these areas, we aim to: (i) gain insight into the cellular underpinnings of network disorders and the mechanisms of neuromodulation; (ii) understand information processing within the networks of patients with motor symptoms, and identify network nodes suitable for therapeutic interventions; (iii) develop innovative and translational neurostimulation algorithms to treat motor symptoms, using personalized and adaptive stimulation methods.We strongly believe that only a unifying, comprehensive, and multidisciplinary effort that brings together experts from neurobiology, neurophysiology, compu¬tational modeling and neuroimaging, mathematics, engineering, psychology, neurology, and neurosurgery has the potential to realize this vision within the coming decade. A structured program to train a new generation of neuroscientists with broad scientific and methodological expertise will strengthen our research efforts. We will simultaneously study experimental interventions in well-described model systems and analyze the mechanisms of established neuromodulation therapies based on quantifiable motor outcomes in patients, for rapid translation from bench to bedside and vice versa. Owing to the breadth of expertise required, this is only possible within the framework of a transregional, multidisciplinary, and collaborative research consortium.

• DFG Programme: CRC/Transregios
• International Connection: Israel

Current projects

• A01 - Mechanisms of disease modification by early deep brain stimulation in a progressive rodent model of Parkinson's disease ‘Earlystim-Rat’ (Project Heads Matthies, Cordula ;  Volkmann, Jens )
• A02 - Mechanisms of gait restoration by mesencephalic stimulation in rat models of cortical and subcortical gait disorders (Project Heads Blum, Robert ;  Schuhmann, Michael ;  Volkmann, Jens )
• A03 - Retuning motor network disorders using neuromodulation of spinal sensory afferents (Project Heads Endres, Matthias ;  Harms, Christoph ;  Wenger, Ph.D., Nikolaus )
• A04 - | Motor cortex plasticity induced by stimulation of the hyperdirect pathway in mice (Project Head Geiger, Jörg )
• A05 - Role of BDNF signaling for striatal plasticity and motor learning (Project Head Sendtner, Michael A. )
• A06 - Central network mechanism of overuse dystonia in genetically-predisposed rodents (Project Heads Ip, Chi Wang ;  Volkmann, Jens )
• B01 - Toward virtual deep brain stimulation (Project Heads Horn, Ph.D., Andreas ;  Ritter, Petra )
• B02 - Local and global neuronal interactions in movement disorders (Project Heads Curio, Gabriel ;  Nikulin, Ph.D., Vadim )
• B03 - Decoding therapy-related inhibition/disinhibition signaling through M1 ECoG and subthalamic LFP real-time classification in patients with Parkinson’s disease (Project Heads Haynes, John-Dylan ;  Neumann, Wolf-Julian )
• B04 - Multisite recordings of basal ganglia-cerebellar-cortical motor circuits in hyperkinetic movement disorders (Project Head Kühn, Andrea )
• B05 - Gait disturbances in Parkinson’s disease: derangements of network dynamics (Project Heads Buck, Andreas ;  Haufe, Stefan ;  Isaias, Ph.D., Ioannis Ugo ;  Volkmann, Jens )
• B06 - Defective interactions of basal ganglia, locus coeruleus, and midbrain circuits for defensive behavior: a model for freezing of gait in PD? (Project Head Tovote, Philip )
• C01 - MEG-based neurophysiological markers of optimized STN-DBS in PD (Project Heads Florin, Esther ;  Schnitzler, Alfons )
• C03 - Closed-loop neurostimulation in MPTP monkeys (Project Head Bergman, Hagai )
• C04 - Advancing neurostimulation to symptom-related individual adaptive stimulation: theoretical models and clinical application (Project Heads Kühn, Andrea ;  Rosenblum, Michael ;  Schneider, Gerd Helge )
• INF - Developing standards for data quality, reproducibility, and accessibility (Project Heads Heuschmann, Peter U. ;  Neumann, Wolf-Julian ;  Preissner, Robert ;  Ritter, Petra ;  Tovote, Philip )
• S01 - Project development of Lead-DBS and advanced field modeling (Project Heads Horn, Ph.D., Andreas ;  van Rienen, Ursula ;  Tietze, Anna )
• Z01 - Central Tasks of the Collaborative Research Centre (Project Head Kühn, Andrea )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin; Julius-Maximilians-Universität Würzburg
• Participating University: Heinrich-Heine-Universität Düsseldorf; Hebrew University of Jerusalem; The Paul Baerwald School of Social Work & Social Welfare; Universität Potsdam; Universität Rostock
• Participating Institution: Bernstein Center for Computational Neuroscience Berlin; Max-Planck-Institut für Kognitions- und Neurowissenschaften
• Spokesperson: Professorin Dr. Andrea Kühn