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Cerebral network function in neurodegeneration: a multimodal approach

English title Cerebral network function in neurodegeneration: a multimodal approach
Applicant Frackowiak Richard
Number 127538
Funding scheme Project funding
Research institution Service de Neurologie Département des Neurosciences Cliniques CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2009 - 31.03.2013
Approved amount 288'000.00
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Keywords (6)

Connectivity; Dysconnection; Magnetization Transfer Imaging; EEG; MCI; MRI

Lay Summary (English)

Lead
Lay summary
English:Key features of Alzheimer's disease (AD), or dementia, seen under the microscope after death include the accumulation of chemicals such as beta-amyloid and tau-protein in the brain. This causes the communication between nerve cells to become disrupted so disturbing thinking and other brain activity.When groups of nerve cells talk to each other in a coordinated manner they generate synchronised activity that we can record with an EEG machine. We believe that it should be possible to detect disturbances of this synchronisation in early AD. If true, EEG recording could become a sensitive and cost-effective diagnostic tool for AD. To this end we have recently developed a new method of EEG analysis. Uniquely, this method provides a detailed map of EEG synchronisation from the whole head. This method is at the heart of our project. We will compare and contrast the EEG results from patients and healthy people with changes in the structure of the brain that we can image with MR scanners and with the clinical state. We also believe we can improve our ability to detect brain damage with the scanner by using a new method of capturing the images, called magnetisation transfer (MT), that are as a consequence clearer and easier to interpret. Both new methods have been tested in preliminary fashion and they work. In this proposal, we will apply both methods to 40 early AD subjects recruited from the Memory Clinic of the Neurology Department at the CHUV in Lausanne, to 40 subjects with Mild Cognitive Impairment (MCI) and to a similar number of matched healthy people. Subjects will be clinically reviewed and re-examined with EEG and scanning over 2-3 years. The EEG and scan data will be correlated with the clinical information.The project is expected to yield evidence of disturbed cortico-cortical communication in early AD. We expect to get an idea of the EEG and scan changes associated with progression over time. We also expect to capture changes associated with the progression from MCI to AD that will occur in a proportion of the MCI patients over the three years of the study. Our statistical analyses will then determine the accuracy and sensitivity of the combined tests as a clinical marker of early AD. Such information should be of importance to treatment strategies designed to target the earliest stages of the disease, possibly before symptoms arise, with the aim of halting or retarding the progress of brain degeneration.French:Les caractéristiques principales de la maladie d'Alzheimer (MA), ou la démence, vues sous microscope après le décès, incluent l'accumulation de substances chimiques comme la bêta-amyloïde et la protéine tau dans le cerveau. Ceci provoque l'interruption de la communication entre les neurones, menant à des troubles de la pensée et d'autres activités du cerveau.Quand des groupes de neurones communiquent entre eux d'une façon coordonnée, ils génèrent une activité synchronisée que nous pouvons enregistrer avec un appareil EEG. Nous croyons qu'il devrait être possible de détecter des perturbations de cette synchronisation dans la MA précoce. Si ceci est vrai, l'enregistrement d'un EEG pourrait devenir un outil de diagnostic sensible et rentable pour la MA. A cet effet, nous avons récemment développé une nouvelle méthode d'analyse EEG. Cette méthode unique fournit une carte détaillée de synchronisation EEG de la tête entière. Cette méthode est au cœur de notre projet. Nous allons comparer et contraster les résultats EEG de patients et de personnes saines présentant des modifications dans la structure du cerveau que nous pouvons imager avec des scanners RM et avec l'état clinique. Nous croyons également que nous pouvons améliorer notre capacité de détecter des troubles cérébraux avec le scanner, en utilisant une nouvelle méthode pour capturer les images, appelée transfert de magnétisation (TM), qui deviennent par conséquence plus claires et plus faciles à interpréter. Ces deux nouvelles méthodes ont été testées d'une façon préliminaire et elles fonctionnent. Dans cette proposition, nous appliquerons les deux méthodes à 40 sujets avec une MA précoce, de la Clinique de la mémoire du Département de Neurologie du CHUV à Lausanne, à 40 sujets avec un Déficit cognitif léger (DCL) et à un nombre similaire de personnes saines assorties. Les sujets seront revus cliniquement et réexaminés avec EEG et scan pendant 2-3 ans. Les données de l'EEG et du scan seront corrélées à l'information clinique.Le projet est supposé produire des preuves d'une communication cortico-corticale perturbée dans la MA précoce. Nous prévoyons de nous faire une idée des changements EEG et scan associés à la progression avec le temps. Nous prévoyons également de capturer des modifications associées à la progression du DCL à la MA qui apparaîtra dans une proportion des patients avec DCL pendant les trois années de l'étude. Nos analyses statistiques détermineront alors la précision et la sensibilité des tests combinés comme marqueur clinique d'une MA précoce. Ces informations devraient être importantes pour les stratégies de traitement désignées à cibler les étapes les plus précoces de la maladie, éventuellement avant l'apparition des symptômes, avec comme objectif d'arrêter ou de retarder la progression de la dégénération du cerveau.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Evolution of source EEG synchronization in early Alzheimer's disease.
Knyazeva Maria G, Carmeli Cristian, Khadivi Alireza, Ghika Joseph, Meuli Reto, Frackowiak Richard S (2013), Evolution of source EEG synchronization in early Alzheimer's disease., in Neurobiology of aging, 34(3), 694-705.
Synchronizability of EEG-based functional networks in early Alzheimer's disease.
Tahaei Marzieh S, Jalili Mahdi, Knyazeva Maria G (2012), Synchronizability of EEG-based functional networks in early Alzheimer's disease., in IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engin, 20(5), 636-41.
EEG-Based Functional Brain Networks: Does the Network Size Matter?
Amir Joudaki A. Salehi N. Jalili M. Knyazeva M.G. (2012), EEG-Based Functional Brain Networks: Does the Network Size Matter?, in PloS one, 7(4), e35673-e35673.
Demyelination of superficial white matter in early Alzheimer's disease: a magnetization transfer imaging study.
Fornari Eleonora, Maeder Philippe, Meuli Reto, Ghika Joseph, Knyazeva Maria G (2012), Demyelination of superficial white matter in early Alzheimer's disease: a magnetization transfer imaging study., in Neurobiology of aging, 33(2), 428.e7-428.e19.
Inhibition in early Alzheimer's disease: an fMRI-based study of effective connectivity.
Rytsar Romana, Fornari Eleonora, Frackowiak Richard S, Ghika Joseph A, Knyazeva Maria G (2011), Inhibition in early Alzheimer's disease: an fMRI-based study of effective connectivity., in NeuroImage, 57(3), 1131-9.
Constructing brain functional networks from EEG: partial and unpartial correlations.
Jalili Mahdi, Knyazeva Maria G (2011), Constructing brain functional networks from EEG: partial and unpartial correlations., in Journal of integrative neuroscience, 10(2), 213-32.
Topography of EEG multivariate phase synchronization in early Alzheimer's disease.
Knyazeva Maria G, Jalili Mahdi, Brioschi Andrea, Bourquin Isabelle, Fornari Eleonora, Hasler Martin, Meuli Reto, Maeder Philippe, Ghika Joseph (2010), Topography of EEG multivariate phase synchronization in early Alzheimer's disease., in Neurobiology of aging, 31(7), 1132-44.
Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults
Knyazeva Maria G., Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults, in Neural Plasticity.

Collaboration

Group / person Country
Types of collaboration
Medical informatics, Computer sciences, EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Department of Computer Engineering, Sharif University of Technology, Tehran Iran (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Hong Kong Polytechnic University Hongkong (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Service of Old Age Psychiatry, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois (C Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Department of Electrical and Computer Engineering, RMIT, Melbourne Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
Neuropsychology and Neurorehabilitation Service, Centre Hospit Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Symposium lecture, European Winter Conference on Brain Research 2013 16.01.2013 Brides Les Bains, France
Bordeaux Alzheimer Disease Symposium 05.11.2012 Arcachon, France
2 posters, 42nd annual meeting of the Society for Neuroscience 2012 13.10.2012 New Orleans, USA
European Federation of Neurological Societies 09.09.2012 Stockholm Sweden
Poster, Annual Meeting of the Swiss Society of Neuroscience 2012 03.02.2012 Zurich, Switzerland
Montreal Neurosciences awayday guest lecture 30.01.2012 Montreal
Oral presentation, 21st ANT Burgundy Neuromeeting 2012 25.01.2012 Beaune, France
Lecture 29.11.2011 BioZentrum Basel
Synapsia 11 23.09.2011 Ljubljana Slovenia
3 posters, 17th Annual Meeting of the Organization for Human Brain Mapping 2011 26.06.2011 Québec City, Canada
Neuronus Krakow 25.04.2011 Krakow Poland
Poster, Annual Meeting of the Swiss Society of Neuroscience2011 26.03.2011 Basel, Switzerland
Alzheimer Disease Congress 10.03.2011 Barcelona Spain
Lecture 25.11.2010 Dept of Neurology Zurich
Poster, Lemanic Neuroscience Annual Meeting 2010 29.10.2010 Geneva, Switzerland
Poster, Alzheimer’s Association International Conference on Alzheimer’s disease 2010 10.07.2010 Honolulu, USA
Symposium lecture, NeuroTalk-2010 25.06.2010 Singapore
Oral presentation, 19th ANT Burgundy Neuromeeting 2010 20.01.2010 Beaune, France


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Lake Geneva Innovation Society meeting 29.11.2011 Geneva


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions BioVision Alexandria 2012 International 21.04.2012
Talks/events/exhibitions BioVision Lyon International 28.03.2011
Media relations: radio, television Charlie Rose progamme PBS TV New York USA International 05.12.2011
Talks/events/exhibitions Lecture in association "Autour de la Russie" (Divonne-les-Bains, France) International 29.10.2011
Talks/events/exhibitions Lecture in association "Léman Russe" Western Switzerland 18.11.2011
Talks/events/exhibitions Brain Awareness Clinic Western Switzerland 09.04.2010
Media relations: radio, television Various Western Switzerland International 12.03.2010

Awards

Title Year
AETAS PRIZE 2011

Associated projects

Number Title Start Funding scheme
133828 Functional and structural connectivity in neurological diseases: an integrated MRI and EEG synchronization approach 01.01.2011 R'EQUIP

Abstract

Key features of Alzheimer’s disease (AD) include the accumulation of beta-amyloid and tau-protein fragments in the brain, the loss or dysfunction of synapses, and the breakdown of the myelin insulation of neuronal fibers. The relationships between these multiple contributing factors are not known. The central hypothesis of the proposed research is that AD-related pathological events disturb the synchronization of cortical activity by synaptic and/or fiber disruption. Since higher cognitive functions are based on distributed synchronized neural networks, synchronization failure is a likely concomitant of cognitive dysfunction in AD patients. The hypothesis predicts that the abnormalities of EEG synchronization in AD patients will be proportional to structural brain damage and to behavioral and cognitive abnormalities.The project’s aim is twofold. At a fundamental level, it is designed to test whether demyelination can be considered a major factor in the AD pathogenesis and whether indeed cognitive decline in AD is correlated with synchronization breakdown. In terms of application, the project is aimed at testing new imaging methods as prospective markers for early diagnostics and for the progression of AD. If the hypothesis is correct, mapping of EEG synchronization has the potential to become a direct outcome measure for clinical trials, which currently use neuropsychological scales for AD. To achieve these goals, we suggest a combination of (1) high-resolution EEG imaging analysed by multivariate synchronization techniques that allow whole-head surface mapping and (2) Magnetization Transfer Imaging (MTI) of the brain with (3) comprehensive clinical examination. The multivariate synchronization techniques proposed here are based on advances in dynamical systems theory and signal processing applied to modern high-resolution EEG (Carmeli et al. 2005). To image the anatomical integrity, we have adapted and improved magnetization transfer magnetic resonance imaging (MT-MRI, Maeder et al. 2005 The Derek Harwood-Nash Award, ASNR 2005). This method permits accurate quantification of regional myelin damage.The challenging task of integrating different technologies is feasible since all the capabilities and clinically-based research facilities needed for the project already exist and are linked together in our institutions (CHUV-FBM-UNIL). Furthermore, available data of the applicants (Frackowiak et al. Knyazeva et al. 2008; Fornari et al. 2008; Knyazeva et al. 2009) demonstrate the significant potential of this combined imaging approach. In particular, both methods reveal AD-relevant abnormalities that turn out to be correlated. Moreover, our findings suggest that there are two phases in AD progression manifested by opposite changes in EEG synchronization against the background of decreasing myelination. They provide specific and testable predictions to be examined in the project.In the proposed 3-year project, 20 AD patients and 40 participants with Mild Cognitive Impairment (MCI) and matched controls will be studied within the frame of baseline cross-sectional (AD vs. Controls) and longitudinal (AD and MCI vs. Controls) studies. The cross-sectional part explores fundamental mechanisms, namely, the impact of anatomical and functional dysconnection on AD pathogenesis. In the longitudinal part, which focuses on the imaging data as a surrogate marker of AD/MCI progression, patients will be clinically reviewed and re-examined with EEG and MTI methods over 2-3 years. To reveal the prognostic value of the imaging data, MCI participants will be retrospectively reclassified into groups of converters and non-converters to AD.The project is expected to yield unique evidence of cortico-cortical connectivity and communication in relation to the clinical AD/MCI picture important for understanding AD mechanisms. Given that the sensitivity and specificity of EEG synchronization mapping will be confirmed, the technique may become useful for improving early diagnosis and treatment strategies for AD and MCI.
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