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ADAPTIVE CLOSED-LOOP CONTROL OF EPILEPTIC SEIZURE SUSCEPTIBILITY


Relevant for Research Area

B - Core Technologies

C - Applications


Summary

The ultimate aim for neurotechnological intervention in epilepsy is to find a strategy by which seizures can be prevented before they arise. This requires continuous indicators of seizure probability and intervention techniques to avert the transition of interictal activity to seizures. Because of intra- and interindividual variability of electrophysiological signatures of epilepsy, such systems should be adaptive and tune in on the optimal settings autonomously.

Using a mouse model of mesial temporal lobe epilepsy (MTLE), one of the most frequent forms of focal epilepsies in adults, we have previously identified biomarkers of seizure probability and severity. These indicators can continuously be determined from electrophysiological recordings with implanted electrodes and can be cross-validated using structural analyses such as histological analysis and Magnetic Resonance Imaging (MRI).

By applying low-frequency stimulation (LFS) to the hippocampal formation, we have demonstrated an effective method for reducing seizure susceptibility in  open-loop stimulation. Concurrently, we have developed a novel method for in vivo closed-loop control of neuronal oscillations, a biomarker of seizure susceptibility.

 


Publications and Achievements

Peer-reviewed publications

Wülfing J., Kumar S.S., Boedecker J., Riedmiller M., Egert U. (2019). Adaptive long-term control of biological neural networks with deep reinforcement learning. Neurocomputing 342:66-74.

Janz P., Hauser P., Heining K., Nestel S., Kirsch M., Egert U., Haas C.A. (2018). Position- and time-dependent Arc expression links neuronal activity to synaptic plasticity during epileptogenesis. Frontiers Cell Neurosci 12:244.

Kilias A., Canales A., Froriep U.P., Park S., Egert U., Anikeeva P. (2018b). Optogenetic entrainment of neural oscillations with hybrid fiber probes. J Neural Eng 15:056006.

Canales A., Park S., Kilias A., Anikeeva P. (2018). Multifunctional fibers as tools for neuroscience and neuroengineering. Acc Chem Res, 51:829;838.

Kilias A., Häussler U., Heining K., Froriep U.P., Haas C.A., Egert U. (2018a). Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model. Hippocampus 28:375–391.

Janz P., Schwaderlapp N., Heining K., Häussler U., Korvink J.G., von Elverfeldt D., Hennig J., Egert U., LeVan P., Haas C.A. (2017b). Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy. eLife 6:e25742.

Janz P., Savanthrapadian S., Häussler U., Kilias A., Nestel S., Kretz O., Kirsch M., Bartos M., Egert U., Haas C.A. (2017a). Synaptic remodeling of entorhinal input contributes to an aberrant hippocampal network in temporal lobe epilepsy. Cereb Cortex, 27:2348–2364.

Häussler U., Rinas K., Kilias A., Egert U., Haas C.A. (2016). Mossy fiber sprouting and pyramidal cell dispersion in the hippocampal CA2 region in a mouse model of temporal lobe epilepsy. Hippocampus, 26:577–588.

Orcinha C., Münzner G., Gerlach J., Kilias A., Follo M., Egert U., Haas C.A. (2016). Seizure- Induced motility of differentiated dentate granule cells is prevented by the central Reelin fragment. Front Cell Neurosci, 10:1–13.

Kumar S.S., Wülfing J., Okujeni S., Boedecker J., Riedmiller M., Egert U. (2016). Autonomous optimization of targeted stimulation of neuronal networks. PLoS Comput Biol 12(8): e1005054.

Heizmann S., Kilias A., Ruther P., Egert U., Asplund M. (2016). Active control of dye release for neuronal tracing using PEDOT-PSS coated electrodes. IEEE Trans Neural Syst Rehabil Eng, 4320:1–9.

 

Other publications Submitted manuscripts

Heining, K., Kilias, A., Janz, P., Häussler, U., Kumar, A., Haas, C.A., Egert, U. (2019). High incidence of weak epileptiform bursts during the inter-ictal phase indicates reduced seizure susceptibility in epileptic mice. (Submitted to eNeuro, currently under revision).

Paschen E, Elgueta, Heining K, Vieira D, Häussler U1, Orcinha C1, Bartos M, Egert U, Janz P*, Haas CA* (2019). Optogenetic low-frequency stimulation of dentate granule cells prevents ictogenesis in experimental epilepsy

Posters

Heining, K., Kilias, A., Kumar, A., Egert, U. (2018). Beyond spikes and seizures: Detecting patterns in epileptiform activity. Bernstein Conference. Berlin, Germany.

Janz, P., Hauser, P., Heining, K., Kirsch, M., Egert, U., Haas, C.A. (2018). Position- and time-dependent Arc expression links neuronal activity to synaptic plasticity during epileptogenesis. FENS – 11th Forum of Neuronscience. Berlin, Germany.

Kilias, A., Häussler, U., Heining, K., Schirmer, M., Haas, C. A., Egert U. (2018). Theta rhythm frequency strongly decreases throughout the epileptic hippocampal formation. FENS – 11th Forum of Neuroscience. Berlin, Germany.

Paschen, E., Janz, P., Vieira, D., Heining, K., Häussler, U., Kilias, A., Egert, U., Haas, CA. (2018). Optogenetic stimulation inhibits seizure generation in a mouse model of mesial temporal lobe epilepsy. FENS – 11th Forum of Neuroscience. Berlin, Germany.

Heining, K., Kilias, A., Janz, P., Häussler, U., Kumar, A., Haas, C. A., Egert U. (2018). Context matters: The role of weak epileptiform bursts in seizure susceptibility. OIST Computational Neuroscience Course (OCNC). Okinawa, Japan.

Vieira, D., Paschen, E., Janz, P., Heining, K., Kilias, A., Häussler, U., Haas, CA., Egert, U. (2018). Adaptive closed-loop control of epileptic seizure susceptibility. Dutch Institute of Systems and Control Summer School in Machine Learning for Control. The Hague, Netherlands.

Vieira, D., Paschen, E., Janz, P., Heining, K., Kilias, A., Häussler, U., Haas, CA., Egert, U. (2018). Adaptive closed-loop control of epileptic seizure susceptibility. International Conference on Advanced Neurotechnology (ICAN 2018). Ann Arbor, USA.

Heining, K., Janz, P., Kilias, A., Haas, C. A., Egert U. (2017). More mild epileptic bursts indicate reduced susceptibility to seizures. Bernstein Conference. Göttingen, Germany.

Safavieh, E., Egert, U. (2017). Structural properties of burst origination and termination regions in simulated neural networks. Bernstein Conference. Göttingen, Germany.

Safavieh, E., Egert, U. (2017). Neuronal connectivity options along the edge of bounded neural networks – Analysis of network structure and dynamics. Bernstein Conference. Göttingen, Germany.

Kilias, A., Canales A., Froriep, U. P., Park, S., Egert U., Anikeeva, P. (2017). Entrainment of neural oscillations by modulating light stimulation. OptoDBS. Geneva, Switzerland.

Heining, K., Janz, P., Kilias, A.,Haas, C. A., Egert U. (2017). Detailed classification of epileptiform activity reveals anti-correlation between severe and mild epileptic bursts. 12th Göttingen Meeting of the German Neuroscience Society. Göttingen, Germany.

Janz, P., Schwaderlapp, N., Heining, K., Häussler, U., Korvink, J.G., von Elverfeldt, D., Hennig, J., Egert, U., LeVan, P., Haas, C.A. (2017). Non-invasive imaging of early tissue damage and subsequent microstructural reorganization predicts the severity of hippocampal sclerosis in mesial temporal lobe epilepsy. 12th Göttingen Meeting of the German Neuroscience Society. Göttingen, Germany.

Kilias, A., Häussler, U., Heining, K., Haas, C. A., Egert U. (2017). Slowing of theta band activity in the epileptic hippocampal formation. 12th Göttingen Meeting of the German Neuroscience Society. Göttingen, Germany.

Safavieh, E., Egert, U. (2016). On the structural properties of burst origination and termination regions in simulated neural networks. Bernstein Conference. Berlin, Germany.

Janz, P., Hauser, P., Heining, K., Nestel, S., Kretz, O., Kirsch, M., Egert, U., Haas, C.A. (2016). Region-specific activity changes during epileptogenesis determine subcellular Arc mRNA localization and synaptic plasticity of dentate granule cells. Copenhagen, Denmark.

Kilias, A., Häussler, U., Heining, K., Kumar, A., Froriep, U. P., Haas, C. A., Egert U. (2016). Theta rhythm impaired in the epileptic hippocampal formation. FENS – 10th Forum of Neuroscience. Copenhagen, Denmark.

 

Talks

Wülfing, J. (2018) Controlling biological neural networks with deep reinforcement learning. In Proc. of the 26th European Symposium on Artificial Neural Networks, Computational Intelligence and Machine Learning, Bruges (Belgium), 25–27 April 2018).

Janz, P. (2017). Imaging epileptogenesis - non-invasive MRI metrics predict the severity of hippocampal sclerosis. Spring Hippocampal Research Conference. Taormina, Italy.

Egert, U. (2018). Autonomous Optimization of Targeted Stimulation of Neuronal Networks. Neurotechnology Summer School, Genova, Italy