P265 Bifurcations and bursting in the Epileptor
Maria Luisa Saggio*1, Viktor Jirsa1
1Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France
*Email: maria-luisa.saggio@univ-amu.fr
Introduction
Large-scale patient-specific models could provide clinicians with an additional tool for the evaluation of the best surgery strategy for drug-resistant epileptic patients, leveraging on the possibility of revealing otherwise hidden complex network and dynamical effects, testing clinical hypotheses, or finding unbiased optimal surgery strategies. One of these frameworks, the Virtual Epileptic Patient (VEP), is currently undergoing validation in a prospective clinical trial involving over 300 patients. It employs the Epileptor [1], a phenomenological mesoscopic model for the most common seizure class, defined in terms of the onset/offset bifurcations marking the transitions between interictal and ictal states are modeled as bifurcations.
Methods
The Epileptor onset/offset bursting class is known in the literature in dynamical systems as square-wave bursting. In this study [2], we utilize insights from a more generic model for square-wave bursting, based on the unfolding of a high codimension singularity, to guide the bifurcation analysis of the Epileptor and gain a deeper understanding of the model and the role played by its parameters. We use analytical methods, numerical continuation of bifurcation curves and model simulations.
Results
We identify a key region in parameter space of topological equivalence between the two models and demonstrate how the Epileptor’s parameters can be modified to produce activities for other seizure classesas predicted by the generic model approach.. Finally, we reveal how the interaction with an additional mechanism for spike-and-wave discharges present in the Epileptor alters the bifurcation structure of the main burster pushing it across a sequence of Supercritical Hopf bifurcations that modulate the oscillatory activity typical of the ictal state.
Discussion
Exploring the full potential of the Epileptor model in terms of bursting dynamics and understanding how to set the parameters to obtain different classes is an important step to (i) enhance our understanding of the model at the core of the VEP framework and (ii) explore the possibility of further personalizing the VEP model. In fact, patients may experience seizures compatible with classes other than square-wave [3]. While the impact of the class on the VEP outcome has not yet been investigated, we know that different classes may exhibit variations in synchronization and propagation properties, warranting further exploration.
Acknowledgements
This research has received funding from EU’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreements No. 101147319 (EBRAINS 2.0 Project).
References
[1]Jirsa, V. K., Stacey, W. C., Quilichini, P. P., Ivanov, A. I., & Bernard, C. (2014). On the nature of seizure dynamics.Brain,137(8), 2210-2230.
[2]Saggio, M. L., & Jirsa, V. (2024). Bifurcations and bursting in the Epileptor.PLOS Computational Biology,20(3), e1011903.
[3] Saggio, M. L., Crisp, D., Scott, J. M., Karoly, P., Kuhlmann, L., Nakatani, M., ... & Stacey, W. C. (2020). A taxonomy of seizure dynamotypes.Elife,9, e55632.
