THEMATIC AREA C

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: Analysis, modeling, and modulation of the human motor network during recovery from motor stroke
Prof. Dr. Christian Gerloff
Dept. of Neurology, UKE

The overall goal of this project is to understand adaptive changes of the cerebral motor network after stroke. In the first funding period, a central multimodal stroke database has been created and various network analyses have been implemented (DCM for fMRI/EEG, graph and game theory, machine learning, oscillator models). In the second funding period, different types of network characterization will be compared and related to clinical parameters. To move on towards causal relations between network dynamics and behavior, we will modulate networks with non-invasive brain stimulation, measure the effects, and apply modeling to predict them. With this thematic continuation and extension into modeling, modulation, and simulation, the project will move towards network-based, individualized outcome prediction and therapeutical applications.
Project C2: Impact of alterations and therapeutic modulation of brain perfusion on structural and functional brain connectivity
PD Dr. Götz Thomalla
Dept. of Neurology, UKE
Prof. Dr. Jens Fiehler
Dept. of Neuroradiology, UKE  

The impact of both alterations as well as therapeutic modulation of brain perfusion on brain connectivity is poorly understood. We will use structural and functional magnetic resonance imaging, perfusion imaging, and EEG to characterize the interaction of brain perfusion, structural and functional brain connectivity in patients with cerebral small vessel disease and healthy control subjects. We will further study the impact of therapeutic modulation of brain perfusion in patients with high-grade carotid artery stenosis by serial measurements before and after revascularization. 
Project C5: Modulation of the action selection and error processing networks in genetic parkinsonism using rTMS and DBS
Prof. Dr. Alexander Münchau
Dept. of Neurology, University of Lübeck
Prof. Dr. Christine Klein
Dept. of Neurology, University of Lübeck  

In the first funding period, we delineated neurophysiological abnormalities in the action selection network in genetically undefined, Parkin- and PINK1-associated parkinsonism, and dopa-responsive dystonia as a function of the dopaminergic state. In X-linked dystonia-parkinsonism, characterised by neurodegeneration in parts of the error processing network, intracortical inhibition was increased. We now propose to modulate the action selection and error processing network with repetitive TMS and deep brain stimulation to explore network dynamics in these patients using EEG.
Project C6: Modulation of disturbed networks in schizophrenia with transcranial electrical stimulation
Prof. Dr. Christoph Mulert
Dept. of Psychiatry, UKE

This project aims at modulating neural mechanisms involved in the pathophysiology of schizophrenia by means of non-invasive brain stimulation. Here, patients will be investigated with EEG, MEG, fMRI and DTI. Simultaneous EEG-fMRI will help characterizing the effects of frontal tDCS. Moreover, we will use a task requiring interhemispheric information transfer which is related to gamma-band phase coupling and auditory verbal hallucinations. During the task we will apply in-phase and anti-phase gamma-band tACS to left and right auditory cortex in order to manipulate interhemispheric gamma-band coupling. EEG will be recorded at the same time. In a similar way, brain function during cognitive tasks will be investigated.
Project C7 : Augmentation of neuronal network plasticity in schizophrenia
Prof. Dr. Jürgen Gallinat
Prof. Dr. Simone Kühn
Dept. of Psychiatry, UKE

Current pathophysiological models of schizophrenia focus on dysconnectivity of distributed neuronal systems to explain the multitude of psychic symptoms. However, therapeutic strategies targeting this specific pathobiology are lacking. Our recent work provides strong evidence that complex video-game training interventions facilitate fronto-hippocampal structural and functional connectivity within 2 months in healthy subjects. The planned project transfers this knowledge into a training study in schizophrenic patients to counteract disease-related dysconnectivity. Underlying mechanisms and behavioral effects are extensively parametrized by resting state fMRI, DTI, MRS, MEG and clinical short- and long-term outcome.
Project C8: Multi-scale assessment and modulation of cortico-subcortical networks in Parkinson´s disease
PD Dr. Monika Poetter-Nerger
Dept. of Neurology, UKE
Dr. Christian Moll
Dept. of Neurophysiology and Pathophysiology, UKE

The aim of this project is to assess and modulate human motor and associative-limbic networks in patients with Parkinson´s disease undergoing deep brain stimulation. A motor task consisting of stepping movements and a cognitive task comprising an auditory gambling paradigm will be performed during and following deep brain surgery. Multi-site activity will be measured in subcortico-cortical networks by intraoperative microelectrode recordings, as well as postoperative EEG, MEG, EMG and pupillometry. The identified networks will be modulated by high-frequency stimulation of the subthalamic area. We expect to find task-related changes of coherent oscillations between cortico-subcortical sites which might be differentially modulated by deep brain stimulation.
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