*Title*: Neuro-inspired macroscale model of tCS-induced changes on epileptic networks

*Context*. Epilepsy refers to a neurological disorder that affects about 1% of the general population. Recent findings indicate that non-invasive brain transcranial current stimulation (tCS) is safe and of therapeutic promise in epilepsy. However, it is not yet indicated as a standard treatment due to major scientific limitations: unknown mechanisms of action, insufficient account for patient-specific factors, poor understanding of short- and long-term effects. The ambition of the GALVANI Project (ERC-SyG 2019; 2020-26) is to transform the care of a large fraction of patients living with drug-resistant epilepsies by solving a fundamental problem: to efficiently target and control large-scale epileptic brain networks with tCS-induced neuromodulatory weak electric fields.

*Rationale. *Electrical stimulation (supra-threshold) and neuromodulation (sub-threshold) are two different methods that can be used to alter brain plasticity in order to lower hyperexcitability and subsequently decrease the occurrence of epileptiform events. These events are generated large-scale brain networks involving interconnected distant brain regions characterized by an increase of excitability. In this context, computational models are an efficient way to understand features of epileptiform events recorded in patients, either intracerebrally or from electrodes located on the scalp. In addition, it is an efficient tool to analyze the impact of tCS on the brain and optimize its therapeutic effect.

*Objective. *This research focuses on neuromodulation induced by transcranial current stimulation (tCS). The objective of the proposed PhD position is to design a neuro-inspired macroscale model of the brain that will simulate electroencephalographic (EEG) signals under 2 conditions: spontaneous activity and tCS. The model will be able to simulate the activity of epileptogenic networks generating epileptic spikes during interictal periods. It will account for immediate (acute) and lasting (short- or long-term) effects of neuromodulatory weak electric fields, which remain elusive. Simulations will help the design of tCS-based neuromodulation strategies aimed at lowering interictal epileptic spikes.

*Methods. *The model will start from previous results of the team (Merlet et al. PlosOne 2013, Bensaid et al. Frontiers in Neuroscience 2019). It will consist of a macroscale network of interconnected (edges) neural populations (nodes) located in the neocortex. Neurophysiological activity of each node will be generated by a neural mass model. The whole model will allow for simulation of normal and epileptic EEG activity (interictal spikes, ictal activity) under 2 conditions: spontaneous and tCS. Simulated signals will be compared to EEG signals recorded in patients under similar conditions. The model will be embedded into an existing software named COALIA developed in Python. tCS induced E-fields will be simulated using SimNibs (to start with) and with tools developed at Neuroelectrics. Optimal parameters reducing epileptic activity will be determined.

*Scientific environment. *GALVANI involves three partners: LTSI-Inserm (Rennes), AMU-APHM (Marseille) and Neuroelectrics (Barcelona). It is intended to develop the next generation of brain stimulation solutions. GALVANI can be viewed as a distributed lab (Rennes-Barcelona-Marseille) working under a common policy to ensure coherence of research and intense collaboration and cross-fertilization. Fellows will be co-supervised in a unique, shared environment with exposure to science, technology and clinical experience.

*Candidate profile.* The research project is at the interface between biomathematics (neuro-inspired models), biophysics (electric field models), and neuroscience/neurology (epilepsy). The candidate will preferably have some background in dynamical systems, computational neuroscience/systems biology or in electrical engineering, with experience in bio-signal processing and biophysics. Knowledge in electrophysiology and/or EEG analysis would be an asset. The PhD fellow will join a multidisciplinary team including research scientists in biomedical engineering, neurophysiological modeling, bio-physics, signal processing, electrophysiology, neurology.

- *Contract*. The position will start on 01/10/2022. The contract is for 3 years with possible extension (3 months). The salary will be defined according to Inserm rules regarding doctoral student remuneration. Deadline for application. 15/07/2022 Contact. Applicants must send a CV and a cover letter to:

Fabrice Wendling (DR Inserm, LTSI, France) Email: fabrice.wendling@inserm.fr

Isabelle Merlet (CR Inserm, LTSI, France) Email: isabelle.merlet@inserm.fr

Elif Koksal (Post-doc fellow, LTSI, France) Email: elif.koksal-ersoz@inserm.fr

Pascal Benquet (Prof. Univ-Rennes1) Email: Pascal.Benquet@univ-rennes1.fr