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Identifying new markers of interictal epileptic activity in humans

English title Identifying new markers of interictal epileptic activity in humans
Applicant Vulliémoz Serge
Number 141165
Funding scheme Project funding (Div. I-III)
Research institution Unité de Neurosonologie Service de Neurologie HUG
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.10.2012 - 30.09.2016
Approved amount 496'551.00
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Keywords (4)

Neuronal networks; Epilepsy; Electroencephalopraphy; functional MRI

Lay Summary (English)

Lead
Lay summary

Epilepsy is a frequent chronic neurological condition affecting around 1% of the general population. It is accompanied by severe disability, related to seizures, as well as associated cognitive and psychiatric disorders. In the majority of epilepsies, seizures are initiated in one localised region of the brain (focal epilepsy) and then spread to other regions. However, epileptic activity is increasingly considered to reflect the abnormal function of a neuronal network comprising several regions rather than one single brain region. The interactions within the network allow the initiation and spread of epileptic activity. Epileptic activity affecting the brain cortex is only partially detected by scalp electroencephalography (EEG) in the form of epileptic discharges and new markers for the epileptic activity between seizures (interictal activity) are needed to achieve a better understanding of how epileptic activity affects brain functions, notably with respect to cognition.

We will investigate functional brain networks non-invasively in humans with different brain imaging techniques based on recording abnormal electrical activity of the brain: 1) Electric Source Imaging (ESI) that estimates the cerebral generators of electrical activity recorded on the scalp using high density EEG; 2) simultaneous EEG and functional magnetic resonance imaging (EEG-fMRI) that maps regions involved in epileptic activity over the whole brain. The combination of these techniques allows studying epileptic activity in the brain with a unique spatial and temporal resolution.

This project builds on our recent work that contributed to mapping the key regions involved in such networks. The first goal is to better understand the interaction between the electrical activity (EEG) and the haemodynamic changes (fMRI) (negative or early fMRI changes related to epileptic activity). The second goal is to investigate how the presence of these epileptic networks alters neuronal networks that are responsible for normal brain functions. The third goal is to understand how regions of the epileptic network interact with each other and how these interactions are modified by the occurrence of epileptic discharges.

The identification of new bio-markers of epileptic activity using multimodal imaging with high spatial and temporal resolution would help monitor disease activity and decide whether more aggressive treatment is needed in order to minimize cognitive impairment. Moreover, in selected patients with pharmaco-resistant seizures, surgical removal of a well-identified epileptic focus, sometimes after intracranial EEG recordings, can lead to seizure-freedom. A comprehensive understanding of the organisation of the epileptic network is crucial for the success of surgery.  On another level, the follow-up of patients after surgery and/or the results intracranial EEG recordings for the delineation of their epileptic focus offer a unique validation for new neuro-imaging techniques in humans.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study.
Coito Ana, Genetti Melanie, Pittau Francesca, Iannotti Giannina R, Thomschewski Aljoscha, Höller Yvonne, Trinka Eugen, Wiest Roland, Seeck Margitta, Michel Christoph M, Plomp Gijs, Vulliemoz Serge (2016), Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study., in Epilepsia, 57(3), 402-11.
EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy.
Coan Ana C, Chaudhary Umair J, Frédéric Grouiller Umair J, Campos Brunno M, Perani Suejen, De Ciantis Alessio, Vulliemoz Serge, Diehl Beate, Beltramini Guilherme C, Carmichael David W, Thornton Rachel C, Covolan Roberto J, Cendes Fernando, Lemieux Louis (2016), EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy., in Journal of neurology, neurosurgery, and psychiatry, 87(6), 642-9.
Epileptic networks are strongly connected with and without the effects of interictal discharges.
Iannotti Giannina R, Grouiller Frédéric, Centeno Maria, Carmichael David W, Abela Eugenio, Wiest Roland, Korff Christian, Seeck Margitta, Michel Christoph, Pittau Francesca, Vulliemoz Serge (2016), Epileptic networks are strongly connected with and without the effects of interictal discharges., in Epilepsia, 57(7), 1086-96.
Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI.
Chaudhary Umair J, Centeno Maria, Thornton Rachel C, Rodionov Roman, Vulliemoz Serge, McEvoy Andrew W, Diehl Beate, Walker Matthew C, Duncan John S, Carmichael David W, Lemieux Louis (2016), Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI., in NeuroImage. Clinical, 11, 486-93.
Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children.
Centeno Maria, Tierney Tim M, Perani Suejen, Shamshiri Elhum A, StPier Kelly, Wilkinson Charlotte, Konn Daniel, Banks Tina, Vulliemoz Serge, Lemieux Louis, Pressler Ronit M, Clark Christopher A, Cross J Helen, Carmichael David W (2016), Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children., in PloS one, 11(2), 0149048-0149048.
Presurgical brain mapping in epilepsy using simultaneous EEG and functional MRI at ultra-high field: feasibility and first results.
Grouiller Frédéric, Jorge João, Pittau Francesca, van der Zwaag Wietske, Iannotti Giannina Rita, Michel Christoph Martin, Vulliémoz Serge, Vargas Maria Isabel, Lazeyras François (2016), Presurgical brain mapping in epilepsy using simultaneous EEG and functional MRI at ultra-high field: feasibility and first results., in Magma (New York, N.Y.), 29(3), 605-16.
Yield of MRI, high-density electric source imaging (HD-ESI), SPECT and PET in epilepsy surgery candidates.
Lascano Agustina M, Perneger Thomas, Vulliemoz Serge, Spinelli Laurent, Garibotto Valentina, Korff Christian M, Vargas Maria I, Michel Christoph M, Seeck Margitta (2016), Yield of MRI, high-density electric source imaging (HD-ESI), SPECT and PET in epilepsy surgery candidates., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 127(1), 150-5.
All-in-one interictal presurgical imaging in patients with epilepsy: single-session EEG/PET/(f)MRI.
Grouiller Frédéric, Delattre Bénédicte M A, Pittau Francesca, Heinzer Susanne, Lazeyras François, Spinelli Laurent, Iannotti Giannina R, Seeck Margitta, Ratib Osman, Vargas Maria I, Garibotto Valentina, Vulliemoz Serge (2015), All-in-one interictal presurgical imaging in patients with epilepsy: single-session EEG/PET/(f)MRI., in European journal of nuclear medicine and molecular imaging, 42(7), 1133-43.
Dynamic directed interictal connectivity in left and right temporal lobe epilepsy.
Coito Ana, Plomp Gijs, Genetti Mélanie, Abela Eugenio, Wiest Roland, Seeck Margitta, Michel Christoph M, Vulliemoz Serge (2015), Dynamic directed interictal connectivity in left and right temporal lobe epilepsy., in Epilepsia, 56(2), 207-17.
Mapping epileptic activity: sources or networks for the clinicians?
Pittau Francesca, Mégevand Pierre, Sheybani Laurent, Abela Eugenio, Grouiller Frédéric, Spinelli Laurent, Michel Christoph M, Seeck Margitta, Vulliemoz Serge (2015), Mapping epileptic activity: sources or networks for the clinicians?, in Frontiers in neurology, 5, 218-218.
Pulse artifact detection in simultaneous EEG-fMRI recording based on EEG map topography.
Iannotti Giannina R, Pittau Francesca, Michel Christoph M, Vulliemoz Serge, Grouiller Frédéric (2015), Pulse artifact detection in simultaneous EEG-fMRI recording based on EEG map topography., in Brain topography, 28(1), 21-32.
Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.
Lemkaddem Alia, Daducci Alessandro, Kunz Nicolas, Lazeyras François, Seeck Margitta, Thiran Jean-Philippe, Vulliémoz Serge (2014), Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging., in NeuroImage. Clinical, 5, 349-58.
EEG source imaging of brain states using spatiotemporal regression.
Custo Anna, Vulliemoz Serge, Grouiller Frederic, Van De Ville Dimitri, Michel Christoph (2014), EEG source imaging of brain states using spatiotemporal regression., in NeuroImage, 96, 106-16.
Electric source imaging of interictal activity accurately localises the seizure onset zone.
Mégevand Pierre, Spinelli Laurent, Genetti Mélanie, Brodbeck Verena, Momjian Shahan, Schaller Karl, Michel Christoph M, Vulliemoz Serge, Seeck Margitta (2014), Electric source imaging of interictal activity accurately localises the seizure onset zone., in Journal of neurology, neurosurgery, and psychiatry, 85(1), 38-43.
Functional brain networks in epilepsy: recent advances in noninvasive mapping.
Pittau Francesca, Vulliemoz Serge (2014), Functional brain networks in epilepsy: recent advances in noninvasive mapping., in Current opinion in neurology, 28(4), 338-43.
Head model and electrical source imaging: a study of 38 epileptic patients.
Birot Gwénael, Spinelli Laurent, Vulliémoz Serge, Mégevand Pierre, Brunet Denis, Seeck Margitta, Michel Christoph M (2014), Head model and electrical source imaging: a study of 38 epileptic patients., in NeuroImage. Clinical, 5, 77-83.
Localization of the epileptogenic tuber with electric source imaging in patients with tuberous sclerosis.
Kargiotis Odysseas, Lascano Agustina M, Garibotto Valentina, Spinelli Laurent, Genetti Melanie, Wissmeyer Michael, Korff Christian M, Momjian Shahan, Michel Christoph M, Seeck Margitta, Vulliemoz Serge (2014), Localization of the epileptogenic tuber with electric source imaging in patients with tuberous sclerosis., in Epilepsy research, 108(2), 267-79.
The role of functional neuroimaging in pre-surgical epilepsy evaluation.
Pittau Francesca, Grouiller Frédéric, Spinelli Laurent, Seeck Margitta, Michel Christoph M, Vulliemoz Serge (2014), The role of functional neuroimaging in pre-surgical epilepsy evaluation., in Frontiers in neurology, 5, 31-31.
Mapping interictal epileptic discharges using mutual information between concurrent EEG and fMRI.
Caballero-Gaudes César, Van de Ville Dimitri, Grouiller Frédéric, Thornton Rachel, Lemieux Louis, Seeck Margitta, Lazeyras François, Vulliemoz Serge (2013), Mapping interictal epileptic discharges using mutual information between concurrent EEG and fMRI., in NeuroImage, 68, 248-62.

Collaboration

Group / person Country
Types of collaboration
EEG and epilepsy Unit, University Hospitals of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Neurorehabilitation clinics, University Hospitals of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dpt of Bioengineering, Ecole Polytechnique Fédérale de Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dpt of Computer Sciences, University of Rome, La Sapienza Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Epilepsy Imaging group, UCL Institute of Neurology, London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
UCL Institute of Child Health, London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Neurology Dpt, Brno Hospitals Czech Republic (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Functional Brain Mapping Lab, University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Awards

Title Year
best poster award. conference:Basic Applied and Clinical Imaging 2015
best poster award Swiss Neurosurgery Society meeting 2014
Young Investigator Award International League Against Epilepsy 2014
Bizot Prize for best Privat Docent thesis, University of Geneva 2013
Poster award and Travel grant international epilepsy conference, Montreal, Canada 2013

Associated projects

Number Title Start Funding scheme
169198 Local and global brain connectivity alterations in focal epilepsy: Effects of disease, surgery and neuromodulation 01.02.2017 Project funding (Div. I-III)
124089 Imaging large scale neuronal networks in epilepsy 01.05.2009 SPUM

Abstract

The aim of this research project is to identify new electrophysiological bio-markers of interictal activity in patients with epilepsy. Cognitive impairment in patients with epilepsy is associated with interictal epileptiform discharges (spikes) on EEG but is also observed in patients without spikes and without brain lesion. This suggests that some interictal activity, yet undetected with scalp electrodes, is altering the functioning of physiological brain networks. Moreover, the neurovascular coupling between epileptic activity and haemodynamic (BOLD) changes in the brain, as measured with simultaneous EEG-fMRI, is still poorly understood, notably regarding BOLD changes starting before the detection of spikes and the presence of negative BOLD changes. Recent studies showed that EEG topography and EEG informed fMRI analysis In this project we propose 3 Workpackages for an in-depth characterization of the interictal state in patients with focal epilepsy using high density EEG, simultaneous EEG-fMRI and intracranial EEG:1)Temporal dynamics of the interictal state. We hypothesize that the analysis of scalp EEG topography will reveal previously undetected neuro-electric changes preceding the spikes. These effects might be related to the time of onset and sign of the spike-related BOLD changes and we will investigate the cortical correlates of such activity with simultaneous intracranial and scalp EEG.2)Interaction between epileptic activity and physiological networks. We hypothesize that combined analysis of epileptic and physiological EEG topography will improve the characterization of epileptic networks and the alteration in physiological networks, as mapped by simultaneous EEG-fMRI. We will investigate whether epileptic networks activity present coherent haemodynamic fluctuations beyond those associated with spikes. 3)Interictal brain connectivity. We hypothesize that functional brain connectivity estimated with high density scalp EEG will be altered in the epileptic network and that dynamic changes will be observed before and during the occurrence of spikes. These changes will be validated with connectivity measures applied to intracranial EEG recording and compared to fMRI connectivity measures in the same patients. The applicant and his collaborators have expertise in high density EEG and EEG-fMRI in epilepsy imaging. The identification of such bio-markers and invasive validation in patients with epilepsy will help solve major issues in epilepsy imaging and will be highly beneficial for the neuro-scientists who use these techniques in other applications. New interictal bio-markers might help monitor disease activity decide whether interictal activity justifies more aggressive treatment in order to minimize cognitive impairment.
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