Research

Theoretical background of our experimental work is the hypothesis that correlated firing of neurons may provide a solution to the problem of integrating distributed information in the brain. Specifically, our work aims at testing the idea that neuronal synchronization may be crucial for the formation of functionally coherent neural states and for response selection in sensorimotor systems. In case of the visual system, where most of our studies have been focussed on, such a mechanism might serve for the binding of information processed in different cortical areas, supporting the formation of coherent percepts. In support of this "temporal binding model", we have observed correlated firing of neurons over large distances within visual cortical areas, between cortical areas and even between the two cerebral hemispheres. Furthermore, we have been able to demonstrate that neural synchrony in visual cortex depends on whether the cells are actually responding to the same object. In addition, we have studied the properties and stimulus-dependence of fast neuronal oscillations at frequencies of 30 to 70 Hz, which reflect the coherent activity of local neuronal groups and are frequently associated with the occurrence of synchrony
between spatially separate cortical sites.

Meanwhile, we have made considerable efforts to generalize these findings which initially were made in the cat. To this end, we have carried out comparative studies of oscillatory activity and neuronal synchronization in the visual system of various carnivore and rodent species. Moreover, we have been able to obtain evidence for the functional relevance of neural synchrony. Thus, we could show that perceptual deficits in cats with strabismic amblyopia are specifically associated with a loss of correlated neuronal firing. Moreover, using the paradigm of binocular rivalry we could demonstrate that, in awake cats, perceptual dominance of a stimulus is accompanied by an enhanced synchronziation in the respective neuronal populations. In addition, we have been interested in studying similar phenomena in subcortical structures. In several projects, we have investigated interactions between cortex and the superior colliculus and the possible role of these corticotectal interactions for the generation of orienting responses in awake animals. Finally, we have extended our work beyond the visual system and started to test the idea of interactions between different sensory modalities (visual, somatosensory and auditory) as well as the potential role of correlated neural firing for sensorimotor integration. Approaching these issues involves the use of behaving animals with chronically implanted electrodes.

The research of the Dept. of Neurophysiology and Pathophysiology currently focuses on several closely related topics:

• Information processing in the visual, auditory and tactile system
• Dynamics of sensori-motor assemblies
• Role of synchronization and oscillations for binding processes
• Role of temporal binding for intermodal and sensorimotor integration
• Mechanisms of plasticity and neural development
• Theories of perception and action
• Role of action in cognitive processing
• Neural correlates of top-down processing, attention, consciousness
• Clinical applications of models of neural dynamics (neurological and psychiatric disorders; pain research; cochlear implants; deep brain stimulation)
• Technical applications of models of neural dynamics (bioinspired robot architectures; brain-computer interfaces)

Several of these issues are addressed in in-vivo experiments on carnivores and rodents. We are currently running eight in-vivo laboratories for studies in anesthetized and behaving animals. To assure transfer of the results to the human brain, we have established two labs for high-density (64-/128-channel) EEG recordings. Moreover, the institute accomodates a MEG lab with a 275-channel CTF whole-head system. The EEG and MEG measurements are combined with fMRI studies carried out both at the University Medical Center Eppendorf as well as in cooperation with several other groups. Moreover, we are performing invasive microelectrode recordings in patients with neurological disorders. These studies, which are carried out as part of a cooperation with the Dept. of Neurosurgery and the Dept. of Neurology at the University Medical Center Eppendorf, allow us to test clinical implications of the temporal binding hypothesis.

Our current projects can be summarized as follows:

• Neural synchrony in cortical and subcortical systems of carnivores and rodents: Experiments in both anesthetized and behaving animals are carried out to test the functional relevance of neural synchronization for sensory processing in the visual, tactile and auditory modality, as well as for cross-modal binding and interactions between neocortex and hippocampus. The studies in awake animals involve multisite recordings with chronically implanted electrodes to allow the direct monitoring of assemblies during performance of behavioural tasks.
  
  
• Studies in transgenic mice: We use the mouse as a model system for investigation of the cellular mechanisms that lead to the buildup of temporal patterns in neural responses and to oscillations in various frequency bands. To this end, baseline data obtained in wildtype-animals are compared to data from mutant strains supposed to show deficits in temporal patterns. Candidates include transgenic animal lines with modified transmitter receptors such as e.g., AMPA, mGluR, GABAA receptors, with modified gap-junctions as well as with altered expression of Kv-channels or cell adhesion molecules. Conditional knock-downs will be used to test the effect of channel modifications by recording from the same animals before and after transgene expression.
  
  
• Neural dynamics in human sensory, motor, cognitive and memory systems: The in-vivo animal studies are complemented by measurements in humans to clarify the extent to which conclusions can be generalized to the human brain and to test the pathophysiological relevance of temporal binding mechanisms. Currently, some of the hypotheses developed on the basis of animal data are tested in humans using EEG, MEG and fMRI, with specific focus on the relation between synchronization phenomena and perceptual, attentional and memory processes. In particular, we investigate the role of temporal binding mechanisms for cross-modal interactions in the human brain. Furthermore, the relation between neural synchrony and conscious awareness is explored.
  
  
• Pathophysiological relevance of neural coherence: In cooperation with neurosurgeons, intraoperative microelectrode recordings are performed in the basal ganglia and thalamic nuclei. The recordings are carried out in patients with Parkinson's Disease, idiopathic dystonia or essential tremor to improve the depth localization of the target sites for deep brain stimulation. Moreover, the data collected during these measurements are used to test hypotheses on the pathophysiological role of neural synchronisation phenomena in these disorders. Complementing the intraoperative recordings, we are also studying animal models of the respective diseases.
  
  
• Robotics applications of the dynamic binding model: As part of several cooperations supported by the EU, we are involved in projects implementing robot systems that combine visual and tactile, or visual and auditory information processing to achieve orienting behaviour, object recognition, navigation, and memory formation. The projects combine a synthetic biorobotics approach with neurophysiological experiments in animals and humans, and computational modeling that allows to identify relevant information processing principles.
  
  
• Interdisciplinary philosophical work: As a complement to the physiological aspects of our research, we are interested in the conceptual and philosophical implications of neurobiological results and in the fundamental discussion of the contributions that empirical neuroscience can make to theories of perception, cognition and action. Currently, a major focus of my work is to trace implications of the temporal binding theory for uncovering the neural correlates of consciousness.