Ph. D. Project
Neuromodulation of epileptic and cognitive network in the visual ventral stream using transcranial electrical stimulation based on reciprocity principle.
2018/09/01 - 2021/09/01
Other supervisor(s):
Imbalance of neuronal excitability is one of the most important cause of diseases (Parkinson disease, epilepsy, psychiatric and mental disorders, etc.) and cognitive impairments (memory, language, motor, emotions, etc.). Electrical brain stimulation, that consist in weak current injection in the cortex, allows to excite or inhibit the neuronal population (Reato et al., 2013 ; Rahman et al., 2017). Thus, electrical brain stimulation allows to deregulate some pathologic electrical mechanisms or at the opposite to restore a function that is needed for physiological cognitive mechanisms. The most important and well-known application concerns the deep brain stimulation in Parkinson disease (Benabid, Nature Med., 2014). In the epilepsy surgery investigation, the intracerebral stimulations temporarily modulates the neuronal networks and especially those are included in specific cognitive networks (Jonas et al., 2012, 2014 ; Trebuchon et al., 2016). This permits to define an individualized functional brain cartography.
In a less invasive way, brain electrical stimulation can be applied on scalp surface. This method, called transcranial, shows very interesting results in several applications (Chrysikou et al., 2017) despite the large diffusion of the electric field within the brain. This large electrical diffusion is due to several methodological aspects: 1. the low number of stimulating electrodes (n=2, one anode and one cathode); 2. The unvalidated calibration of biophysical models (in-vivo human head conductivities are unknown); 3. The stimulation parameters (electrode positions and stimulation intensity) comes from numerical simulations.
Thanks to the development of more precise scalp EEG recordings (Koessler et al., 2015) and technical development of non-invasive transcranial device, a new non-invasive transcranial stimulation method that is more precise and efficient appears. This method is called closed-loop stimulation. It relies on the following purpose: the electrical path between scalp and brain is the same for stimulation and recording. In a theoretical point of view, this method relies on reciprocity theory (Dmochowski et al., 2011, 2017). Thanks to several scalp electrodes, it is possible to inject within the brain the same electrical field that was generated by a brain source. This reciprocity method allows: 1. to focus more efficiently the stimulation and avoid the stimulation of neighboring brain regions; 2. to reduce the intensity of scalp stimulation and thus to avoid the side effects.
At present, two main problems remains in order to verify our main hypothesis that is: reciprocity transcranial electrical stimulation reliably modulates the electrophysiological activity of brain networks when the electric field is focused onto the site of EEG generation.
The first problem consists in the human in-vivo validation of the reliability of brain targeting using reciprocity transcranial electrical stimulation.
The second problem consists in the characterization of the neuromodulation using the electrophysiological signals (patterns, topography) and also behavioral responses (reaction time, efficiency).
Two studies will be tackled:
1. Is it possible to modulate the amplitude and the frequency of the epileptic discharges that comes from a neuronal hyperexcitability?
2. Is it possible to modulate the evoked electrophysiological responses using fast visual periodic stimulation in visual recognition tasks?
We will focus our studies in the temporo-occipital region (visual ventral stream). This brain region is currently the main focus of our neuroscientific lab project and also very adapted for scalp stimulation due to the proximity with the scalp electrodes.

Originality and strength of this project rely on:
1. The use of reciprocity transcranial electrical brain stimulation that very few laboratories in worldwide are able to manage. City College of New-York is one of them.
2. The use of simultaneous scalp EEG, intracerebral EEG (SEEG), fast periodic visual stimulations and reciprocity electrical brain stimulations (tCS). Only the University Hospital in Nancy are able to perform that kinds of synchronous recordings and stimulations.
3. The human model we will study. Indeed focal drug-resistant epilepsy are one of the rare diseased that allows EEG-SEEG-tCS recordings.

Methods of this PhD will be developed as follows: first, targeting the dedicated brain regions. To do that, we will record and analyze the electrical scalp projection of controlled intracerebral electrical stimulations (site, amplitude and frequency). The real leadfiled matrix (leadfield) coming from these stimulations will be calculated and then we will be able to define the reciprocity stimulation parameters (scalp electrode positions and stimulation intensity) using inverse problem methods. For each patient, two different brain targets will be chosen: one target in the epileptic network that produces interictal epileptic discharges (individually designed) and one target in the cognitive network that gives evoked responses to the FPVS (OFA, FFA, STS, ...). In all, twelve patients will be included in this PhD study.
The expected results are the electrophysiological characterization of the reciprocity transcranial electrical stimulation. In other words, we want to demonstrate in human in-vivo that this non-invasive stimulation is focal and intense in the brain target and not outside. In that way, we will analyze the frequency, the power and the amplitude of the intracerebral EEG signals in order to quantify the stimulation effect in the brain target and the surrounding areas. We also want to demonstrate that this non-invasive stimulation, especially cathodal stimulation, can inhibit an epileptic brain network. An amplitude and frequency decrease should be observed using a hyperpolarizing stimulation (cathodal). A quantitative comparison between high number intracerebral epileptic discharges (n>100) before, during and after transcranial stimulations should show significant differences. Finally we want to demonstrate that this non-invasive stimulation can module a cognitive network (visual ventral stream). We will use the amplitude and the anatomical distribution of the evoked intracerebral responses (frequency tagged) before, during and after the non-invasive reciprocity stimulations.
neuromodulation, neuronal networks, epilepsy, cognition, transcranial electrical stimulation
Duration : 36 months
Employer : PhD grant from France (France allocation)
Location : Pavillon Krug, Hôpital Central, Nancy, FRANCE
Health, Biology and Signal department of CRAN, UMR7039 : ESPaCE project
Wage : env. 1700 euros brut (France allocation)
Expected background : neurosciences expertise with a internship of at least 6 months in a neurscience lab ; skills in biomedical engineering, signal and image processing in neurosciences, instrumentation and sensors, neurophysiology
Joined Phd with the City College of New-York is currently under evaluation. Dr. Jacek Dmochowski (PI, biomedical engineering department, NY) already gives his agreement to support this request.
Biology, Signals and Systems in Cancer and Neuroscience
France PhD grant (ministery allocation)