THEMATIC AREA A

3rd FUNDING PERIOD

THEMATIC AREA A: MULTI-SITE COMMUNICATION AS A BASIS OF COGNITION

Projects in thematic area A investigate multi-site interactions in the nervous system subserving visual, auditory, tactile and pain perception, multisensory and sensorimotor integration, attention, as well as emotion and reward processing. Project A1 aims at modelling the large scale dynamics in the ferret and the human brain, based on data from the respective experimental projects. Projects A2 and A3 address multisensory interactions with a focus on visual-auditory and visual-tactile integration, using complementary approaches in animal and human studies. Projects A4, A5 and A6 have a common focus on multi-site interactions in pain perception, focussing on modulation of pain processing by attentional and contextual factors (A4), at network mechanisms of sensitisation and habituation (A5) and at the effects of contextual manipulation of anxiety and reward value (A6).
Project A1: Dynamics and control of multi-site communication in the brain 
Prof. Dr. Claus Hilgetag
Dept. of Computational Neuroscience, UKE

The project aims to understand fundamental mechanisms of network dynamics in intact as well as perturbed and modulated neural networks through computational analysis and modeling, and to apply these insights to specific networks of the ferret and human brain. Two central aspects of multi-site communication will be considered, first, the integration of inter-regional anatomical connectivity with local brain architecture and its implications for normal brain dynamics, and, second, mechanisms of network control and their implications for understanding functional deficits in brains that are pathologically impaired (e.g., by stroke) as well as for the experimental modulation of brain dynamics.
Project A2:  Opto- and chemogenetic modulation of ferret cortical network dynamics 
Prof. Dr. Andreas Engel
Dept. of Neurophysiology and Pathophysiology, UKE  

The project will use optogenetic and chemogenetic approaches to test the relevance of functional coupling for stimulus processing and behavior. Moreover, we will investigate the role of excitatory and inhibitory cell populations for functional coupling. Multisite recordings will be carried out from visual, auditory and parietal areas using electrocorticographic arrays and optrodes. Manipulation of neurons will be achieved by expression of ChR2(ET/TC), iChloC, or a chemogenetic silencer (hM4D). In anesthetized ferrets, we will test effects of manipulation of oscillations and phase coupling on multisensory stimulus processing. In awake behaving ferrets, we will investigate the effects of network manipulation on performance in a stimulus-detection task.
Project A3: Sensorimotor readout of human multisensory networks
Prof. Dr. Andreas Engel
Dept. of Neurophysiology and Pathophysiology, UKE
Dr. Till Schneider
Dept. of Neurophysiology and Pathophysiology, UKE

This project aims at investigating the sensorimotor readout of signals from multisensory networks in rule switching tasks using MEG and EEG. Functional connectivity between sensory and prefrontal/premotor areas underlying flexible sensorimotor mapping and rule switching will be investigated in healthy participants and in patients with Parkinson’s disease (PD) who have impairments in switching of sensorimotor rules. Furthermore, we will modulate sensorimotor mappings and rule switching and their underlying functional networks by transcranial alternating current stimulation (tACS) in healthy participants and by deep brain stimulation (DBS) in PD patients.
Project A5: Characterizing and modulating thalamo-pontine networks in headache
Prof. Dr. Arne May
Dept. of Systems Neuroscience, UKE

The goal of this project is to investigate nociceptive processing focusing on the hierarchical role and structure of brainstem networks in different headache and facial pain syndromes and between the ictal and interictal state building on the results of the previous funding period. Hypothesis-driven experiments will focus on hypothalamic input to lower brainstem nuclei such as the PAG, SSR and trigeminal nuclei. We will subsequently describe cortico-pontine networks using simultaneous brainstem functional MRI and EEG in migraine patients. Finally, we will investigate brainstem networks mediating the trigemino-autonomic reflex and modulate this reflex arc using highly specific interventions such as oxygen inhalation and indomethacin.
Project A6: Temporal and spatial contrast phenomena in pain networks
Prof. Dr. Christian Büchel
Dept. of Systems Neuroscience, UKE

We will build upon novel functional MRI (fMRI) pulse sequences to study the network properties underlying spatial and temporal contrast phenomena in pain. We will further improve cortico-spinal fMRI and perform fMRI network studies and behavioral investigations to test for a spinal contribution to temporal (offset analgesia) and spatial contrast (thermal grill illusion; TGI) phenomena. In addition, we will use fMRI to further investigate the observation that the PAG codes a pain derivative signal and how this signal is integrated into the network of other nociceptive areas such as the secondary somatosensory cortex and the anterior insula.
Project A7: Catecholaminergic modulation of cortical decision networks
Prof. Dr. Tobias Donner
Dept. of Neurophysiology and Pathophysiology, UKE

Inference and decision-making are fundamental cognitive capacities emerging from selective neural interactions within the cerebral cortex. These interactions are under strong control of modulatory inputs from brainstem arousal systems. But a comprehensive framework for the modulation of cortical decision networks is lacking. Here, we aim to develop such a framework for the catecholaminergic (noradrenergic and dopaminergic) modulatory systems of the human brain. To this end, we will unravel the range of catecholamine effects on cortical network dynamics and cognition: from boosting inference through transient catecholamine release, to impairments under sustained, excessive catecholamine release under stress.
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