Skip to main content

Advertisement

SpringerLink
Log in

MEG Connectivity Analysis in Patients with Alzheimer’s Disease Using Cross Mutual Information and Spectral Coherence

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is an irreversible brain disorder which represents the most common form of dementia in western countries. An early and accurate diagnosis of AD would enable to develop new strategies for managing the disease; however, nowadays there is no single test that can accurately predict the development of AD. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain connectivity in terms of linear and nonlinear couplings by means of spectral coherence and cross mutual information function (CMIF), respectively. The variables defined from these functions provide statistically significant differences (p < 0.05) between AD patients and control subjects, especially the variables obtained from CMIF. The results suggest that AD is characterized by both decreases and increases of functional couplings in different frequency bands as well as by an increase in regularity, that is, more evident statistical deterministic relationships in AD patients’ MEG connectivity. The significant differences obtained indicate that AD could disturb brain interactions causing abnormal brain connectivity and operation. Furthermore, the combination of coherence and CMIF features to perform a diagnostic test based on logistic regression improved the tests based on individual variables for its robustness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIGURE 1
FIGURE 2
FIGURE 3
FIGURE 4
FIGURE 5
FIGURE 6

Similar content being viewed by others

References

  1. Achermann, P., and A. A. Borbély. Coherence analysis of the human sleep electroencephalogram. Neuroscience 85:1195–1208, 1998.

    Article  CAS  PubMed  Google Scholar 

  2. Alonso, J. F., M. A. Mañanas, D. Hoyer, Z. L. Topor, and E. N. Bruce. Evaluation of respiratory muscles activity by means of mutual information function at different levels of ventilatory effort. IEEE Trans. Biomed. Eng. 54:1573–1582, 2007.

    Article  PubMed  Google Scholar 

  3. Alonso, J. F., M. A. Mañanas, S. Romero, D. Hoyer, J. Riba, and M. Barbanoj. Drug effect on EEG connectivity assessed by linear and nonlinear couplings. Hum. Brain Mapp. 31:487–497, 2010.

    PubMed  Google Scholar 

  4. Babiloni, C., G. Frisoni, F. Vecchio, R. Lizio, M. Pievani, C. Geroldi, C. Fracassi, F. Vernieri, F. Ursini, G. Rodriguez, F. Nobili, S. Salinari, S. Van Dijkman, R. Ferri, and P. M. Rossini. Global functional coupling of resting EEG rhythms is abnormal in mild cognitive impairment and Alzheimer’s disease: a multicenter EEG study. J. Psychophysiol. 23:224–234, 2010.

    Article  Google Scholar 

  5. Becker, R. E., and N. H. Greig. Alzheimer’s disease drug development in 2008 and beyond: problems and opportunities. Curr. Alzheimer Res. 5:346–357, 2008.

    Article  CAS  PubMed  Google Scholar 

  6. Berendse, H. W., J. P. A. Verbunt, Ph. Scheltens, B. W. van Dijk, and E. J. Jonkman. Magnetoencephalographic analysis of cortical activity in Alzheimer’s disease: a pilot study. Clin. Neurophysiol. 111:604–612, 2000.

    Article  CAS  PubMed  Google Scholar 

  7. Blennow, K., M. J. de Leon, and H. Zetterberg. Alzheimer’s disease. Lancet 368:387–403, 2006.

    Article  CAS  PubMed  Google Scholar 

  8. Buckner, R. L. Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44:195–208, 2004.

    Article  CAS  PubMed  Google Scholar 

  9. Czigler, B., D. Csikós, Z. Hidasi, Z. A. Gaál, É. Csibri, É. Kiss, P. Salacz, and M. Molnár. Quantitative EEG in Alzheimer’s disease patients—power spectrum and complexity features. Int. J. Psychophysiol. 68:75–80, 2008.

    PubMed  Google Scholar 

  10. Cummings, J. L. Alzheimer’s disease. N. Engl. J. Med. 351:56–67, 2004.

    Article  CAS  PubMed  Google Scholar 

  11. Dubois, B., H. H. Feldman, C. Jacova, S. T. Dekosky, P. Barberger-Gateau, J. Cummings, A. Delacourte, D. Galasko, S. Gauthier, G. Jicha, K. Meguro, J. O’brien, F. Pasquier, P. Robert, M. Rossor, S. Salloway, Y. Stern, P. J. Visser, and P. Scheltens. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 6:734–746, 2007.

    Article  PubMed  Google Scholar 

  12. Fernández, A., R. Hornero, A. Mayo, J. Poza, P. Gil-Gregorio, and T. Ortiz. MEG spectral profile in Alzheimer’s disease and mild cognitive impairment. Clin. Neurophysiol. 117:306–314, 2006.

    Article  PubMed  Google Scholar 

  13. Fernández, A., R. Hornero, A. Mayo, J. Poza, F. Maestú, and T. Ortiz. Quantitative magnetoencephalography of spontaneous brain activity in Alzheimer disease: an exhaustive frequency analysis. Alzheimer Dis. Assoc. Disord. 20:153–159, 2006.

    Article  PubMed  Google Scholar 

  14. Fernández, A., A. Turrero, P. Zuluaga, P. Gil, F. Maestú, P. Campo, and T. Ortiz. Magnetoencephalographic parietal delta dipole density in mild cognitive impairment: preliminary results of a method to estimate the risk of developing Alzheimer disease. Arch. Neurol. 63:427–430, 2006.

    Article  PubMed  Google Scholar 

  15. Franciotti, R., D. Iacono, S. Della Penna, V. Pizzella, K. Torquati, M. Onofrj, and G. L. Romani. Cortical rhythms reactivity in AD, LBD and normal subjects. A quantitative MEG study. Neurobiol. Aging 27:1100–1109, 2006.

    Article  CAS  PubMed  Google Scholar 

  16. Gómez, C., R. Hornero, D. Abásolo, A. Fernández, and J. Escudero. Analysis of the magnetoencephalogram background activity in Alzheimer’s disease patients with auto-mutual information. Comput. Methods Programs Biomed. 87:239–247, 2007.

    Article  PubMed  Google Scholar 

  17. Gómez, C., R. Hornero, D. Abásolo, A. Fernández, and J. Escudero. Analysis of MEG background activity in Alzheimer’s disease using nonlinear methods and ANFIS. Ann. Biomed. Eng. 37:586–594, 2009.

    Article  PubMed  Google Scholar 

  18. Gómez, C., R. Hornero, D. Abásolo, A. Fernández, and M. López. Complexity analysis of the magnetoencephalogram background activity in Alzheimer’s disease patients. Med. Eng. Phys. 28:851–859, 2006.

    Article  PubMed  Google Scholar 

  19. Gómez, C., C. J. Stam, R. Hornero, A. Fernández, and F. Maestú. Disturbed beta band functional connectivity in patients with mild cognitive impairment: a MEG study. IEEE Trans. Biomed. Eng. 56:1683–1690, 2009.

    PubMed  Google Scholar 

  20. Hari, R. Magnetoencephalography in clinical neurophysiological assessment of human cortical functions. In: Electroencephalography: Basic Principles, Clinical Applications, and Related Fields, 5th ed., edited by E. Niedermeyer, and F. Lopes da Silva. Philadelphia: Lippincontt Williams & Wilkins, 2005, pp. 1165–1197.

    Google Scholar 

  21. Hornero, R., J. Escudero, A. Fernández, J. Poza, and C. Gómez. Spectral and nonlinear analyses of MEG background activity in patients with Alzheimer’s disease. IEEE Trans. Biomed. Eng. 55:1658–1665, 2008.

    PubMed  Google Scholar 

  22. Hoyer, D., B. Pompe, K. H. Chon, H. Hardraht, C. Wicher, and U. Zwiener. Mutual information function assesses autonomic information flow of heart rate dynamics at different time scales. IEEE Trans. Biomed. Eng. 52:584–592, 2005.

    Article  PubMed  Google Scholar 

  23. Jeong, J. EEG dynamics in patients with Alzheimer’s disease. Clin. Neurophysiol. 115:1490–1505, 2004.

    Article  PubMed  Google Scholar 

  24. Jeong, J., J. C. Gore, and B. S. Peterson. Mutual information analysis of the EEG in patients with Alzheimer’s disease. Clin. Neurophysiol. 112:827–835, 2001.

    Article  CAS  PubMed  Google Scholar 

  25. Jin, S. H., Y. J. Kwon, J. S. Jeong, S. W. Kwon, and D. H. Shin. Increased information transmission during scientific hypothesis generation: mutual information analysis of multichannel EEG. Int. J. Psychophysiol. 62:337–344, 2006.

    Article  PubMed  Google Scholar 

  26. Kalaria, R. N., G. E. Maestre, R. Arizaga, R. P. Friedland, D. Galasko, K. Hall, J. A. Luchsinger, A. Ogunniyi, E. K. Perry, F. Potocnik, M. Prince, R. Stewart, A. Wimo, Z. X. Zhang, P. Antuono, and for the Word Federation of Neurology Dementia Research Group. Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 7:812–826, 2008.

    Article  PubMed  Google Scholar 

  27. Locatelli, T., M. Cursi, D. Liberati, M. Franceschi, and G. Comi. EEG coherence in Alzheimer’s disease. Electroencephalogr. Clin. Neurophysiol. 106:229–237, 1998.

    Article  CAS  PubMed  Google Scholar 

  28. McKhann, G., D. Drachman, M. Folstein, R. Katzman, D. Price, and E. M. Stadlan. Clinical diagnosis of Alzheimer’s disease: report of NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34:939–944, 1984.

    CAS  PubMed  Google Scholar 

  29. Minati, L., T. Edginton, M. G. Bruzzone, and G. Giaccone. Current concepts in Alzheimer’s disease: a multidisciplinary review. Am. J. Alzheimers Dis. Other Demen. 24:95–121, 2009.

    Article  PubMed  Google Scholar 

  30. Montez, T., S. S. Poil, B. F. Jones, I. Manshanden, J. P. Verbunt, B. W. van Dijk, A. B. Brussaard, A. van Ooyen, C. J. Stam, P. Scheltens, and K. Linkenkaer-Hansen. Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease. Proc. Natl Acad. Sci. USA 106:1614–1619, 2009.

    Article  CAS  PubMed  Google Scholar 

  31. Nunez, P. L., B. M. Wingeier, and R. B. Silberstein. Spatial-Temporal structures of human alpha rhythms: microcurrents sources, multiscale elements, and global binding of local networks. Hum. Brain Mapp. 13:125–164, 2001.

    Article  CAS  PubMed  Google Scholar 

  32. Osipova, D., J. Ahveninen, O. Jensen, A. Ylikoski, and E. Pekkonen. Altered generation of spontaneous oscillations in Alzheimer’s disease. Neuroimage 27:835–841, 2005.

    Article  PubMed  Google Scholar 

  33. Osipova, D., J. Ahveninen, S. Kaakkola, I. P. Jääskeläinen, J. Huttunen, and E. Pekkonen. Effects of scopolamine on MEG spectral power and coherence in elderly subjects. Clin. Neurophysiol. 114:1902–1907, 2003.

    Article  CAS  PubMed  Google Scholar 

  34. Poza, J., R. Hornero, D. Abásolo, A. Fernández, and M. García. Extraction of spectral based measures from MEG background oscillations in Alzheimer’s disease. Med. Eng. Phys. 29:1073–1083, 2007.

    Article  PubMed  Google Scholar 

  35. Poza, J., R. Hornero, J. Escudero, A. Fernández, and C. I. Sánchez. Regional analysis of spontaneous MEG rhythms in patients with Alzheimer’s disease using spectral entropies. Ann. Biomed. Eng. 36:141–152, 2008.

    Article  PubMed  Google Scholar 

  36. Rossini, P. M., S. Rossi, C. Babiloni, and J. Polich. Clinical neurophysiology of aging brain: from normal aging to neurodegeneration. Prog. Neurobiol. 83:375–400, 2007.

    Article  CAS  PubMed  Google Scholar 

  37. Schreiber, T., and A. Schmitz. Surrogate time series. Physica D 142:346–382, 2000.

    Article  Google Scholar 

  38. Stam, C. J. Nonlinear dynamical analysis of EEG and MEG: review of an emerging field. Clin. Neurophysiol. 116:2266–2301, 2005.

    Article  CAS  PubMed  Google Scholar 

  39. Stam, C. J. Use of magnetoencephalography (MEG) to study functional brain networks in neurodegenerative disorders. J. Neurol. Sci. 289:128–134, 2010.

    Article  CAS  PubMed  Google Scholar 

  40. Stam, C. J., W. de Haan, A. Daffershofer, B. F. Jones, I. Manschanden, A. M. van Cappellen van Walsum, T. Montez, J. P. Verbunt, J. C. de Munck, B. W. van Dijk, H. W. Berendse, and P. Scheltens. Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer’s disease. Brain 132:213–224, 2009.

    Article  CAS  PubMed  Google Scholar 

  41. Stam, C. J., B. F. Jones, I. Manshanden, A. M. van Cappellen van Walsum, T. Montez, J. P. Verbunt, J. C. de Munck, B. W. van Dijk, H. W. Berendse, and P. Scheltens. Magnetoencephalographic evaluation of resting-state functional connectivity in Alzheimer’s disease. Neuroimage 32:1335–1344, 2006.

    Article  CAS  PubMed  Google Scholar 

  42. Stam, C. J., G. Nolte, and A. Daffertshofer. Phase lag index: assessment of functional connectivity from multichannel EEG and MEG with diminished bias from common sources. Hum. Brain Mapp. 28:1178–1193, 2007.

    Article  PubMed  Google Scholar 

  43. Stam, C. J., A. M. van Cappellen van Walsum, Y. A. L. Pijnenburg, H. W. Berendse, J. C. de Munck, Ph Scheltens, and B. W. van Dijk. Generalized synchronization of MEG recordings in Alzheimer’s disease: evidence for involvement of the gamma band. J. Clin. Neurophysiol. 19:562–574, 2002.

    Article  PubMed  Google Scholar 

  44. van Cappellen van Walsum, A.-M., Y. A. L. Pijnenburg, H. W. Berendse, B. W. van Dijk, D. L. Knol, Ph Scheltens, and C. J. Stam. A neural complexity measure applied to MEG data in Alzheimer’s disease. Clin. Neurophysiol. 114:1034–1040, 2003.

    Article  PubMed  Google Scholar 

  45. Weiss, S., and P. Rappelsberger. Long-range EEG synchronization during word encoding correlates with successful memory performance. Brain Res. Cogn. Brain Res. 9:299–312, 2000.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Asociación de Enfermos de Alzheimer (AFAL) for supplying the patients who have participated in this study. CIBER-BBN is an initiative of the Instituto de Salud Carlos III, Spain. This study was partially supported by the following contract grant sponsors: Subdirección General de Proyectos de Investigación, Ministerio de Ciencia e Innovación, Spain, Contract Grant Nos. TEC2008-02241 and TEC2008-02754; European Social Funds, European Union, Contract Grant No. MTM2005-08519-C02-01.

Author information

Authors and Affiliations

  1. Department of Automatic Control (ESAII), Biomedical Engineering Research Centre (CREB), Universitat Politècnica de Catalunya (UPC), Carrer Pau Gargallo 5, 08028, Barcelona, Spain

    Joan Francesc Alonso, Miguel Ángel Mañanas & Sergio Romero

  2. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain

    Joan Francesc Alonso, Miguel Ángel Mañanas & Sergio Romero

  3. Biomedical Engineering Group, Department T.S.C.I.T., E.T.S. Ingenieros de Telecomunicación, Universidad de Valladolid, Valladolid, Spain

    Jesús Poza & Roberto Hornero

  4. Centro de Magnetoencefalografía Dr. Pérez-Modrego, Universidad Complutense de Madrid, Madrid, Spain

    Alberto Fernández

Authors
  1. Joan Francesc Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jesús Poza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel Ángel Mañanas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sergio Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alberto Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roberto Hornero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joan Francesc Alonso.

Additional information

Associate Editor Nathalie Virag oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alonso, J.F., Poza, J., Mañanas, M.Á. et al. MEG Connectivity Analysis in Patients with Alzheimer’s Disease Using Cross Mutual Information and Spectral Coherence. Ann Biomed Eng 39, 524–536 (2011). https://doi.org/10.1007/s10439-010-0155-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-010-0155-7

Keywords

Search

Navigation