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July 2020 to June 2024
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, computational 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.
Find the TRR on GEPRIS.
Gait disturbances are a severe burden for Parkinson’s disease patients, and respond poorly to therapies including deep brain stimulation (DBS) of the subthalamic nucleus. In particular, standard continuous stimulation may prevent dynamic integration of the cortical-subcortical information needed to adapt gait patterns to the environment. We will combine cortical and subcortical recordings, molecular brain imaging, and kinematic measurements in a virtual reality environment to characterize the dynamic cortical-subthalamic neural control of human gait and its derangements during freezing of gait (FOG). Our setup will also allow us to explore the feasibility of online FOG detection as an important translational use case for new devices that constantly adapt DBS-controlled electrical impulses to gait-related neural signals.
Find project B05 on GEPRIS.