Connectivity; Dysconnection; Magnetization Transfer Imaging; EEG; MCI; MRI
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.
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.
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.
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.
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.
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.
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.
Knyazeva Maria G., Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults, in Neural Plasticity
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.