THEMATIC AREA C

3rd FUNDING PERIOD

THEMATIC AREA C: ALTERED MULTI-SITE COMMUNICATION IN BRAIN DISORDERS

Thematic area C focuses on disorders that are associated with pathological alteration in neuronal interactions. The clinical conditions addressed in the projects of this thematic area include stroke, Parkinson’s disease and schizophrenia. Projects C1, C2 and C4 involve studies on patients suffering from stroke, focussing on the analysis of interactions between cortical motor regions and on mechanisms of large-scale functional regeneration and reorganisation. In these projects, structural and functional coupling are investigated in a complementary manner in the same patient groups. Project C5 addresses alterations of multi-site interactions and of structural connectivity between cortical motor regions in patients with a monogenetic form of Parkinson’s disease. Project C6 investigates changes in multi-site interactions occurring in patients with schizophrenia.
Project C1: Encoding of kinematics and effector choice in reorganized brain networks after stroke
Prof. Dr. Christian Gerloff
Dept. of Neurology, UKE

The results of the past funding periods point towards parieto-frontal connectivity as a crucial element in recovery of motor function after stroke. Now, we aim to apply our findings to more complex motor behavior and cognitive processes like decision making in stroke patients. To this end, we will combine kinematics, structurally informed EEG network metrics, virtual-reality based interventions and network modulation by transcranial AC stimulation. Moreover, for the first time the spinal motoneuron pool (measured by functional MRI) will be integrated into network models in order to improve their robustness and predictive properties. With this thematic continuation and extension towards behavioral relevance, targeted network modulation and improved modeling, the project will move on towards network-based therapeutic interventions in stroke.
Project C2: Structural determinants of disturbed evidence accumulation in cortical decision networks after stroke 
PD Dr. Bastian Cheng
Dept. of Neurology, UKE
Prof. Dr. Götz Thomalla
Dept. of Neurology, UKE

The evidence accumulation process during decision making is distributed over a large-scale structural and functional network of cortical regions. However, fundamental questions concerning the organization and structural determinants of this network remain open. We will study stroke patients and patients with cerebral small vessel disease, providing models for focal and distributed brain lesions, by algorithmic modeling of behavior, structural MRI, EEG, and catecholaminergic pharmacologic intervention. By this, we aim at a better understanding of the structural underpinnings and organization of the cortical decision network in the healthy brain, and of cognitive impairments in patients with vascular brain lesions.
Project C5: Characterization of action control networks in genetically determined parkinsonism
Prof. Dr. Alexander Münchau
Dept. of Neurology, University of Lübeck
Prof. Dr. Christine Klein
Dept. of Neurology, University of Lübeck  

In the first two funding periods, we found evidence for increased activity of action selection networks in patients with genetically undefined parkinsonism, Parkin- and PINK1-associated parkinsonism, L-dopa-responsive dystonia, and X-linked dystonia parkinsonism. We now focus on network-related processes leading to disease manifestation by comparing asymptomatic mutation carriers with symptomatic patients with Parkin- and PINK1-associated parkinsonism, X-linked dystonia parkinsonism, and GBA-associated parkinsonism. To this end, we will use behavioral tasks, EEG, TMS, pupillometry, and neuromelanin-sensitive high-resolution MRI.
Project C6: Pharmacological and electrical modulation of disturbed networks in schizophrenia and the clinical high-risk state for psychosis
Prof. Dr. Christoph Mulert
Center of Psychiatry, Justus-Liebig University, Giessen
PD Dr. Gregor Leicht
Dept. of Psychiatry and Psychotherapy, UKE

This project aims to investigate the effects of both pharmacological modulation and transcranial AC stimulation (tACS) on alterations of connectivity patterns in different stages of schizophrenia and in the ketamine model of schizophrenia using EEG and simultaneous EEG and fMRI. Theta-tACS will target disturbed patterns of functional brain connectivity within a working-memory network related to schizophrenia cognitive symptoms. The glutamatergic intervention at the NMDA-receptor using glycine will be used to modulate alterations of (1) the gamma-band connectivity between auditory cortices related to the occurrence of auditory hallucinations and (2) a gamma-band-specific network involved in deficits in attentional auditory information processing.
Project C7 : Effects of virtual reality in the augmentation of neuronal network plasticity
Prof. Dr. Jürgen Gallinat
Dept. of Psychiatry, UKE
Prof. Dr. Simone Kühn
Dept. of Psychiatry, UKE

A main finding of the previous funding period was that brain-plasticity effects in the hippocampal-prefrontal network in response to a video game intervention are primarily induced by demanding spatial navigation (training of a 3D versus 2D version of the same video game). Clinical data of schizophrenia patients show a significant decrease in general psychopathology in the 3D training condition. Based on this encouraging evidence our goal for the next funding period is to (1) maximize the plasticity effects by using virtual-reality technology in the game, (2) unravel the time course and sequence of network plasticity effects and (3) to search for predictors of long-term plasticity in functional connectivity measures prior to training.
Project C8: Cognitive and motor networks as a basis of mobility in patients with Parkinson´s disease 
PD Dr. Monika Poetter-Nerger
Dept. of Neurology, UKE
PD Dr. Christian Moll
Dept. of Neurophysiology and Pathophysiology, UKE

The aim of this project is to advance multi-scale assessments of functional connectivity of cognitive and motor neuronal circuits to daily relevant tasks related to mobility in Parkinson´s disease patients, driving and walking. Intraoperative and postoperative recordings of neuronal network activities will be performed under realistic conditions, combining a driving simulator setup, virtual reality, mobile EEG, wearable movement-tracking sensors and eye-tracking techniques. Modulation of network activities will be performed by applying novel algorithms of deep brain stimulation such as patterned stimulation with evaluation of its impact on behavioral performance and assessment of reshaped subcortico-cortical network activity.
Project C9: Multiscale modeling of network dynamics: from multimodal data to biophysical mechanisms and individual predictions (NEW: 2019)
Prof. Dr. Petra Ritter
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology, Berlin Institute of Health (BIH), Bernstein Center for Computational Neuroscience, Berlin

This project develops and applies a computational framework that will enable the integration of neuroscience data across multiple scales to identify general principles of their interactions. We propose an approach using multiscale analyses of empirical neuroimaging data available from the SFB projects and large-scale brain simulations with TheVirtualBrain (TVB). We will decompose complex brain dynamics into probabilistic functional modes and mathematically operationalize them as manifolds along which trajectories evolve as the dynamics unfold.
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