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.

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.

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.

Prof. Dr. Andreas Engel – Dept. of Neurophysiology and Pathophysiology, UKE
Dr. Till Schneider – Dept. of Neurophysiology and Pathophysiology, 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.

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.

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.

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.

This project aims at the modulation of multisensory networks by using electrical epicortical stimulation in the ferret. In the first funding period, we have investigated cortico-cortical as well as cortico-subcortical interactions using combinations of electrocorticographic and laminar probe recordings. These networks will now be modulated using electrical stimulation through an electrocorticographic grid. We will aim at demonstrating effects of electrical entrainment in both acute and chronically implanted ferrets. By manipulation of network dynamics we aim at testing the functional role of oscillations and functional connectivity and the relevance of different types of functional coupling. Furthermore, we will model the observed effects of electrical stimulation on assembly dynamics.

This project aims at modulation of visuotactile multi-site interactions using transcranial alternating current stimulation (tACS) in combination with EEG recordings. tACS provides a promising approach for entrainment of cortical oscillations and modulation of frequency-specific coupling across cortical assemblies. Therefore, this approach has potential for probing the causal relevance of oscillatory coupling in perceptual and cognitive processes. The planned experiments will build on studies of multisensory networks carried out in the first SFB funding phase. We will aim at modulating resting and task-related functional connectivity in both intra- and interhemispheric networks in order to test hypotheses on the role of oscillations and functional connectivity. Modulation effects will be modeled in cooperation with other SFB projects.

Prof. Dr. Andreas Engel – Dept. of Neurophysiology and Pathophysiology, UKE
Prof. Dr. Peter König – Institute of Cognitive Science, University of Osnabrück  

The goal of this project is to investigate nociceptive processing focusing on the hierarchical role and structure of brainstem networks in the physiological and pathophysiological state, i.e., in different headache and facial pain syndromes as well as between the ictal and interictal state. Using pharmacological intervention (unspecific pain medication and headache-specific medication) we will modulate these hierarchical network patterns of nociceptive brainstem nuclei and eventually combine simultaneous brainstem fMRI and cortical EEG recordings to characterize cortico-pontine networks in pain transmission and control.

Previous studies have unequivocally demonstrated the power of the antinociceptive system in endogenously controlling pain. This system comprises interacting regions such as the rostral ventromedial medulla, the periaqueductal grey, the insula, and anterior cingulate cortex. The emphasis of the current project is on modulating this antinociceptive network pharmacologically in humans. In the first part of the project we will modulate this network using opioid analgesics (remifentanil) in an open-hidden paradigm. In the second part we will investigate a form of temporal contrast analgesia named „offset analgesia“.

The slow accumulation of evidence about the state of the outside world is a key process in decision-making. Recent observations indicate that this process emerges from flexible interactions within networks of association cortex, critically depends on NMDA-receptors on recurrent synapses, and is adaptively shaped by neuromodulatory brainstem systems. We will test these hypotheses in the human brain. To this end, we will combine selective pharmacological interventions, MEG recordings of cortical network dynamics, and model-based data analyses.

The focus of this project is the attentional consequence of pain in term of its interaction with ongoing pro-cesses. Specifically, we want to elucidate how the different components of the pain experience drive its at-tention demanding properties and to understand where in the brain this critical interaction of the ‘pain ma-trix’ and attentional networks take place. Therefore, we will modulate the perception of physically identical heat pain stimuli by three different contextual manipulations and evaluate the associated attentional conse-quences in a well established paradigm of visual processing. In a fourth part of this project, we will study patients with Parkinson’s disease as a model for disturbed executive function that should result in a dysbal-ance between pain and attentional processes and thus contribute to the high prevalence of chronic pain in this patient group.