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Epileptor: a PhysioNet – TNG collaboration
On the nature of seizure dynamics
Jirsa VK, Stacey WC, Quilichini PP, Ivanov AI, Bernard C.
Brain. 2014 Aug;137(Pt 8):2210-30. doi: 10.1093/brain/awu133
Scientists at the INS – PhysioNet and TNG Teams – and the University of Michigan, USA have shown that epileptic seizures are a primitive form of brain activity common to all species, from flies to Humans. Such activity is always there – potentially – in any healthy brain. Epileptic seizures are coded (or hardwired) in our neuronal networks. They exist in a latent state.
Legend of the image. Geometrically speaking, a seizure is a spiral travelling on a cone. The mathematical rules governing its onset and offset are invariant across species.
Our principal objective is to understand how physiological and pathological behaviors emerge from the organization and the reorganization of the underlying neuronal architecture.
The group’s research is structured around five themes:
- Cell/network dynamics and learning in physiological and pathological conditions (in epileptic patients, monkeys and rodents)
- Mechanisms leading to the construction of an epileptic brain (in epileptic patients, monkeys and rodents)
- Anatomo-functional organization of normal and epileptic networks (in epileptic patients, monkeys and rodents)
- Coupling between metabolism, chloride homeostasis and cell/network function (in rodents)
- (NEW) Neuroengineering: this research field is developed by a new group inside Physionet, lead by Dr. Adam Williamson, recipient of the ERC Starting Grant 2016
Six sub-groups explore different aspects of these themes:
- Human epilepsies (PI: F. Bartolomei)
- Dynamics of cells and networks (PI: C. Bernard)
- Structural and Neurochemical properties of neuronal networks (PI: M. Esclapez)
- Metabolism and Neuroprotection (PI: Y. Zilberter)
- Dynamics of chloride homeostasis (PI: P. Brest)
- Neuroengineering (PI: A. Williamson)
Cognitive processes depend upon the activity of distributed networks in the brain. Our main goal is to further our understanding of the basic rules of neuronal activity in given behavioral states in physiological conditions, and how these rules are modified in epilepsy. Under this theme, we are trying to understand how different brain regions communicate to each other and exchange information, using multisite in vivo recordings in normal and epileptic animals. Brain trajectories are analyzed under various behavioral conditions. This work is done in close collaboration with the TNG team of V. Jirsa. One level down, we are trying to understand how neurons are connected to each other functionally in vivo, using silicon probe recordings in normal and epileptic animals. Our goal is to understand the dynamics of the connectivity maps between the temporal lobe and its connected areas.
One level further down, we are trying to understand the input-output relationship of neurons in vitro, focusing on their intrinsic properties (like resonance), the properties of the synaptic they receive and their morphological features.
Another level down, one principal question is how neuronal activity depends on energy metabolism (Sub-group 4; PI: Y. Zilberter; Metabolism and Neuroprotection). Many neurodegenerative diseases are commonly characterized by metabolic stress. We suggest that metabolic deficits results in a pathological cycle of events, which contribute to the development of neurodegenerative diseases. A key prediction of our hypothesis is that the strategic compensation of energy deficiency could interrupt this pathological spiral and could provide a rational therapeutic option, which addresses the cause of the neurodegenerative diseases and not just the symptoms.
The last level is at the gene/protein level. Based on electrophysiological results, we are trying to understand the rules of protein remapping in epilepsy. We focus on epigenenetics, and we use a pharmacological approach to prevent epileptogenesis and repair the circuitry.
Finally, one part of our activity is devoted to design new in vivo recording devices. This is done in close collaboration with Pr. G. Malliaras from Ecole des Mines de St Etienne à Gardanne. We are experimenting multimodal organic probes, equipped with pre-amplifiers at the recording site. The device is able to record local field potentials with a superior signal to noise ratio. We are now working on the multimodal aspect, to measure simultaneously electrical signals and any enzymatic activity.