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Connectivity factors in neurodegenerative diseases

Principal Investigator: Maria Knyazeva


Overview and research topics

      We are studying the effects of pathological processes on structural and functional aspects of cerebral connectivity. To this end, we implement a multimodal aproach by combining MRI based methods (e.g., Magnetization Transfer Imaging, Fig. 1) and high-density-EEG based techniques (Fig. 2). We are developing new methods of analysis of functional connectivity compatible with MRI-based imaging data. The multivariate EEG synchronization techniques are among such methods. They allow a whole-brain mapping of functional connectivity (Fig. 4) and are readily compatible with the structural imaging data, which is of particular interest for application to distributed brain pathologies like schizophrenia or Alzheimer’s disease (AD).
     In our central project we are testing the myelodegenerative hypothesis of AD. In the brain, the spread of conventional AD markers—beta-amyloid and tau-protein fragments— inversely repeats the order of myelination, which suggests that myelin breakdown is among the key events that ignite the disease. Indeed, recently we have shown that, in mild AD, demyelination of association fibers is stronger in the late-myelinating areas (Fig. 3). The key issues to explore include: Can we detect pre-clinical demyelination? How does demyelination affect functional connectivity, cognitive activity, and behavior in AD? Can individual analysis of structural and/or functional connectivity be useful for early diagnostics and novel therapeutic approaches to AD?
     In other projects, we investigate dysconnection hypothesis of schizophrenia, a role of frontal connectivity in psychogenic nonepileptic seizures, distributed functional networks in cognition. 




Key Publications

Jalili M., Knyazeva MG. EEG-based functional networks in schizophrenia. Computers in Biology and Medicine. 2011

Jalili M., Knyazeva MG. Constructing brain functional networks from EEG: partial vs. unpartial correlations. Journal of Integrative Neuroscience. 2011

Rytsar R, Fornari E, Frackowiak RS, Ghika J and Knyazeva M, "Inhibition in early Alzheimer's disease: an fMRI-based study of effective connectivity", Neuroimage, 2011 in press.

Knyazeva MG, Jalili M, Frackowiak RS, Rossetti AO. Psychogenic seizures and frontal disconnection: EEG synchronisation study. J Neurol Neurosurg Psychiatry. 2011 Mar 14.

Fornari E, Maeder P, Meuli R, Ghika J, Knyazeva MG. Demyelination of superficial white matter in early Alzheimer's disease: a magnetization transfer imaging study. Neurobiol Aging. 2010 Dec 27. [Epub ahead of print]

Knyazeva MG, Carmeli C, Fornari E, Meuli R, Small M, Frackowiak RS, Maeder P.
Binding under Conflict Conditions: State-Space Analysis of Multivariate EEG
Synchronization. J Cogn Neurosci. 2010 Oct 14. [Epub ahead of print].

Knyazeva MG, Jalili M, Brioschi A, Bourquin I, Fornari E, Hasler M, Meuli R, Maeder P, Ghika J. Topography of EEG multivariate phase synchronization in early Alzheimer's disease. Neurobiol Aging. 2010 Jul;31(7):1132-44. Epub 2008 Sep 5.

D. M. Walker, C. Carmeli, F. J. Pérez-Barbería, M. Small and E. Pérez-Fernández. Inferring networks from multivariate symbolic time series to unravel behavioural interactions among animals. Animal Behaviour, 79: 351-359, 2010.

Jalili M, Meuli R, Do KQ, Hasler M, Crow TJ, Knyazeva MG. Attenuated asymmetry of functional connectivity in schizophrenia: a high-resolution EEG study. Psychophysiology. 2010 Jul 1;47(4):706-16. Epub 2010 Jan 22.

De Feo O, Carmeli C. Estimating interdependences in networks of weakly coupled
deterministic systems. Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Feb;77(2 Pt
2):026711. Epub 2008 Feb 27.

Knyazeva MG, Jalili M, Meuli R, Hasler M, De Feo O, Do KQ. Alpha rhythm and hypofrontality in schizophrenia. Acta Psychiatr Scand. 2008 Sep;118(3):188-99. Epub 2008 Jul 10.

Lavoie S, Murray MM, Deppen P, Knyazeva MG, et al.. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology. 2008 Aug;33(9):2187-99. Epub 2007 Nov 14.

Carmeli C, Lopez-Aguado L, Schmidt KE, De Feo O, Innocenti GM. A novel interhemispheric interaction: modulation of neuronal cooperativity in the visual areas. PLoS One. 2007 Dec 12;2(12):e1287.

Fornari E, Knyazeva MG, Meuli R, Maeder P. Myelination shapes functional activity in the developing brain. Neuroimage. 2007 Nov 15;38(3):511-8. Epub 2007 Jul 24.

Jalili M, Lavoie S, Deppen P, Meuli R, Do KQ, Cuénod M, Hasler M, De Feo O, Knyazeva MG. Dysconnection topography in schizophrenia revealed with state-space analysis of EEG. PLoS One. 2007 Oct 24;2(10):e1059.

Knyazeva MG, Fornari E, Meuli R, Maeder P. Interhemispheric integration at different spatial scales: the evidence from EEG coherence and FMRI. J Neurophysiol. 2006 Jul;96(1):259-75. Epub 2006 Mar 29.

Knyazeva MG, Fornari E, Meuli R, Innocenti G, Maeder P. Imaging of a synchronous neuronal assembly in the human visual brain. Neuroimage. 2006 Jan 15;29(2):593-604. Epub 2005 Sep 22.

Carmeli C, Knyazeva MG, Innocenti GM, De Feo O. Assessment of EEG synchronization based on state-space analysis. Neuroimage. 2005 Apr 1;25(2):339-54.

Knyazeva MG, Maeder P, Kiper DC, Deonna T, Innocenti GM. Vision after early-onset lesions of the occipital cortex: II. Physiological studies. Neural Plast. 2002;9(1):27-40.

Innocenti GM, Maeder P, Knyazeva MG, Fornari E, Deonna T. Functional activation of microgyric visual cortex in a human. Ann Neurol. 2001 Nov;50(5):672-6.

Knyazeva MG, Innocenti GM. EEG coherence studies in the normal brain and after early-onset cortical pathologies. Brain Res Brain Res Rev. 2001 Oct;36(2-3):119-28. Review.

Innocenti GM, Kiper DC, Knyazeva MG, Deonna TW. On nature and limits of cortical developmental plasticity after an early lesion, in a child. Restor Neurol Neurosci. 1999;15(2-3):219-27.

Knyazeva MG, Kiper DC, Vildavski VY, Despland PA, Maeder-Ingvar M, Innocenti GM. Visual stimulus-dependent changes in interhemispheric EEG coherence in humans. J Neurophysiol. 1999 Dec;82(6):3095-107. PubMed PMID: 10601444.

Kiper DC, Knyazeva MG, Tettoni L, Innocenti GM. Visual stimulus-dependent changes in interhemispheric EEG coherence in ferrets. J Neurophysiol. 1999 Dec;82(6):3082-94.



- Fonds National Suisse project grant - Synchronization Failure in Alzheimer’s disease: Linking Brain Imaging and the Clinical Picture – 3 years CHF280K

- FNS Re’quip grant - Multimodal approach for in vivo exploration of functional and anatomical connectivity in the human brain – EEG equipment – CHF66K

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