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Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy

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Abstract

Generalized Fixation-off Sensitivity (CGE-FoS) patients present abnormal EEG patterns when losing fixation. In the present work, we studied two CGE-FoS epileptic patients with simultaneous EEG-fMRI. We aim to identify brain areas that are specifically related to the pathology by identifying the brain networks that are related to the EEG brain altered rhythms. Three main analyses were performed: EEG standalone, where the voltage fluctuations in delta, alpha, and beta EEG bands were obtained; fMRI standalone, where resting-state fMRI ICA analyses for opened and closed eyes conditions were computed per subject; and, EEG-informed fMRI, where EEG delta, alpha and beta oscillations were used to analyze fMRI. Patient 1 showed EEG abnormalities for lower beta band EEG brain rhythm. Fluctuations of this rhythm were correlated with a brain network mainly composed by temporo-frontal areas only found in the closed eyes condition. Patient 2 presented alterations in all the EEG brain rhythms (delta, alpha, beta) under study when closing eyes. Several biologically relevant brain networks highly correlated (r > 0.7) to each other in the closed eyes condition were found. EEG-informed fMRI results in patient 2 showed hypersynchronized patterns in the fMRI correlation spatial maps. The obtained findings allow a differential diagnosis for each patient and different profiles with respect to healthy volunteers. The results suggest a different disruption in the functional brain networks of these patients that depends on their altered brain rhythms. This knowledge could be used to treat these patients by novel brain stimulation approaches targeting specific altered brain networks in each patient.

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References

  • Allen, P. J., Josephs, O., & Turner, R. (2000). A method for removing imaging artifact from continuous EEG recorded during functional MRI. NeuroImage, 12(2), 230–239.

    Article  CAS  PubMed  Google Scholar 

  • Beckmann, C. F., DeLuca, M., Devlin, J. T., & Smith, S. M. (2005). Investigations into resting-state connectivity using independent component analysis. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360(1457), 1001–1013.

    Article  PubMed  PubMed Central  Google Scholar 

  • Beckmann, C. F., & Smith, S. M. (2004). Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Transactions on Medical Imaging, 23(2), 137–152.

    Article  PubMed  Google Scholar 

  • Bittar, R. G., Andermann, F., Olivier, A., Dubeau, F., Dumoulin, S. O., Pike, G. B., & Reutens, D. C. (1999). Interictal spikes increase cerebral glucose metabolism and blood flow: a PET study. Epilepsia, 40(2), 170–178.

    Article  CAS  PubMed  Google Scholar 

  • Brigo, F., Rossini, F., Stefani, A., Nardone, R., Tezzon, F., Fiaschi, A., et al. (2013). Fixation-off sensitivity. Clinical Neurophysiology, 124(2), 221–227.

    Article  CAS  PubMed  Google Scholar 

  • Chaudhary, U. J., Duncan, J. S., & Lemieux, L. (2013). Mapping hemodynamic correlates of seizures using fMRI: a review. Human Brain Mapping, 34(2), 447–466.

    Article  PubMed  Google Scholar 

  • Damoiseaux, J. S., Rombouts, S. A., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., & Beckmann, C. F. (2006). Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13848–13853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Bonaventura, C., Vaudano, A. E., Carni, M., Pantano, P., Nucciarelli, V., Garreffa, G., et al. (2005). Long-term reproducibility of fMRI activation in epilepsy patients with fixation off sensitivity. Epilepsia, 46(7), 1149–1151.

    Article  PubMed  Google Scholar 

  • Feige, B., Scheffler, K., Esposito, F., Di Salle, F., Hennig, J., & Seifritz, E. (2005). Cortical and subcortical correlates of electroencephalographic alpha rhythm modulation. Journal of Neurophysiology, 93(5), 2864–2872.

    Article  PubMed  Google Scholar 

  • Formaggio, E., Storti, S. F., Boscolo Galazzo, I., Bongiovanni, L. G., Cerini, R., Fiaschi, A., & Manganotti, P. (2013). Reproducibility of EEG-fMRI results in a patient with fixation-off sensitivity. Clin EEG Neurosci.

  • Goldman, R. I., Stern, J. M., Engel, J., Jr., & Cohen, M. S. (2002). Simultaneous EEG and fMRI of the alpha rhythm. Neuroreport, 13(18), 2487–2492.

    Article  PubMed  PubMed Central  Google Scholar 

  • Iannetti, G. D., Di Bonaventura, C., Pantano, P., Giallonardo, A. T., Romanelli, P. L., Bozzao, L., et al. (2002). fMRI/EEG in paroxysmal activity elicited by elimination of central vision and fixation. Neurology, 58(6), 976–979.

    Article  CAS  PubMed  Google Scholar 

  • Jann, K., Dierks, T., Boesch, C., Kottlow, M., Strik, W., & Koenig, T. (2009). BOLD correlates of EEG alpha phase-locking and the fMRI default mode network. NeuroImage, 45(3), 903–916.

    Article  CAS  PubMed  Google Scholar 

  • Kelly, R. E., Jr., Alexopoulos, G. S., Wang, Z., Gunning, F. M., Murphy, C. F., Morimoto, S. S., et al. (2010). Visual inspection of independent components: defining a procedure for artifact removal from fMRI data. Journal of Neuroscience Methods, 189(2), 233–245.

    Article  PubMed  PubMed Central  Google Scholar 

  • Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Research. Brain Research Reviews, 29(2–3), 169–195.

    Article  CAS  PubMed  Google Scholar 

  • Koutroumanidis, M., Tsatsou, K., Sanders, S., Michael, M., Tan, S. V., Agathonikou, A., & Panayiotopoulos, C. P. (2009). Fixation-off sensitivity in epilepsies other than the idiopathic epilepsies of childhood with occipital paroxysms: a 12-year clinical-video EEG study. Epileptic Disorders, 11(1), 20–36.

    PubMed  Google Scholar 

  • Krakow, K., Baxendale, S. A., Maguire, E. A., Krishnamoorthy, E. S., Lemieux, L., Scott, C. A., & Smith, S. J. (2000). Fixation-off sensitivity as a model of continuous epileptiform discharges: electroencephalographic, neuropsychological and functional MRI findings. Epilepsy Research, 42(1), 1–6.

    Article  CAS  PubMed  Google Scholar 

  • Laufs, H. (2008). Endogenous brain oscillations and related networks detected by surface EEG-combined fMRI. Human Brain Mapping, 29(7), 762–769.

    Article  PubMed  Google Scholar 

  • Laufs, H., Daunizeau, J., Carmichael, D. W., & Kleinschmidt, A. (2008). Recent advances in recording electrophysiological data simultaneously with magnetic resonance imaging. NeuroImage, 40(2), 515–528.

    Article  CAS  PubMed  Google Scholar 

  • Laufs, H., Kleinschmidt, A., Beyerle, A., Eger, E., Salek-Haddadi, A., Preibisch, C., & Krakow, K. (2003). EEG-correlated fMRI of human alpha activity. NeuroImage, 19(4), 1463–1476.

    Article  CAS  PubMed  Google Scholar 

  • Mandelkow, H., Halder, P., Boesiger, P., & Brandeis, D. (2006). Synchronization facilitates removal of MRI artefacts from concurrent EEG recordings and increases usable bandwidth. NeuroImage, 32(3), 1120–1126.

    Article  CAS  PubMed  Google Scholar 

  • Mantini, D., Perrucci, M. G., Del Gratta, C., Romani, G. L., & Corbetta, M. (2007). Electrophysiological signatures of resting state networks in the human brain. Proceedings of the National Academy of Sciences of the United States of America, 104(32), 13170–13175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez, K., Solana, A. B., Burgaleta, M., Hernandez-Tamames, J. A., Alvarez-Linera, J., Roman, F. J., et al. (2013). Changes in resting-state functionally connected parietofrontal networks after videogame practice. Human Brain Mapping, 34(12), 3143–3157.

    Article  PubMed  Google Scholar 

  • Mecarelli, O., Gregori, B., Gilio, F., Conte, A., Frasca, V., Accornero, N., & Inghilleri, M. (2006). Effects of repetitive transcranial magnetic stimulation in a patient with fixation-off sensitivity. Experimental Brain Research, 173(1), 180–184.

    Article  CAS  PubMed  Google Scholar 

  • Michels, L., Bucher, K., Luchinger, R., Klaver, P., Martin, E., Jeanmonod, D., & Brandeis, D. (2010). Simultaneous EEG-fMRI during a working memory task: modulations in low and high frequency bands. PLoS One, 5(4), e10298.

    Article  PubMed  PubMed Central  Google Scholar 

  • Parra, J., Meeren, H. K., Kalitzin, S., Suffczynski, P., de Munck, J. C., Harding, G. F., et al. (2000a). Magnetic source imaging in fixation-off sensitivity: relationship with alpha rhythm. Journal of Clinical Neurophysiology, 17(2), 212–223.

    Article  CAS  PubMed  Google Scholar 

  • Parra, J., Meeren, H. K., Kalitzin, S., Suffczynski, P., de Munck, J. C., Harding, G. F., et al. (2000b). Magnetic source imaging in fixation-off sensitivity: relationship with alpha rhythm. Journal of Clinical Neurophysiology, 17(2), 212–223.

    Article  CAS  PubMed  Google Scholar 

  • Patel, J. K., & Read, C. B. (1996). Handbook of the normal distribution. New York: Marcel Dekker.

    Google Scholar 

  • Patriat, R., Molloy, E. K., Meier, T. B., Kirk, G. R., Nair, V. A., Meyerand, M. E., et al. (2013). The effect of resting condition on resting-state fMRI reliability and consistency: a comparison between resting with eyes open, closed, and fixated. NeuroImage, 78, 463–473.

    Article  PubMed  PubMed Central  Google Scholar 

  • Peca, S., Carni, M., Di Bonaventura, C., Aprile, T., Hagberg, G. E., Giallonardo, A. T., et al. (2010). Metabolic correlatives of brain activity in a FOS epilepsy patient. NMR in Biomedicine, 23(2), 170–178.

    CAS  PubMed  Google Scholar 

  • Smith, S. M., Fox, P. T., Miller, K. L., Glahn, D. C., Fox, P. M., Mackay, C. E., et al. (2009). Correspondence of the brain’s functional architecture during activation and rest. Proceedings of the National Academy of Sciences of the United States of America, 106(31), 13040–13045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solana, A. B., Hernandez-Tamames, J. A., Manzanedo, E., Garcia-Alvarez, R., Zelaya, F. O., & Del Pozo, F. (2014). Gradient induced artifacts in simultaneous EEG-fMRI: Effect of synchronization on spiral and EPI k-space trajectories. Magn Reson Imaging.

  • Srivastava, G., Crottaz-Herbette, S., Lau, K. M., Glover, G. H., & Menon, V. (2005). ICA-based procedures for removing ballistocardiogram artifacts from EEG data acquired in the MRI scanner. NeuroImage, 24(1), 50–60.

    Article  CAS  PubMed  Google Scholar 

  • Strigaro, G., Prandi, P., Varrasi, C., Monaco, F., & Cantello, R. (2011). Cortical excitability changes associated with fixation-off sensitivity: a case report. Epilepsia, 52(8), e89–92.

    Article  PubMed  Google Scholar 

  • Wu, L., Eichele, T., & Calhoun, V. D. (2010). Reactivity of hemodynamic responses and functional connectivity to different states of alpha synchrony: a concurrent EEG-fMRI study. NeuroImage, 52(4), 1252–1260.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuan, H., Zotev, V., Phillips, R., Drevets, W. C., & Bodurka, J. (2012). Spatiotemporal dynamics of the brain at rest–exploring EEG microstates as electrophysiological signatures of BOLD resting state networks. NeuroImage, 60(4), 2062–2072.

    Article  PubMed  Google Scholar 

  • Zuo, X. N., Kelly, C., Adelstein, J. S., Klein, D. F., Castellanos, F. X., & Milham, M. P. (2010). Reliable intrinsic connectivity networks: test-retest evaluation using ICA and dual regression approach. NeuroImage, 49(3), 2163–2177.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Ricardo Bruña and Elena Molina for productive discussions on the applied analysis in this work. Fudnación CIEN-Fundacion Reina Sofia, Centro de Investigación en red Ciber-BBN, projects MADR.IB S-SAL-312-2006 by Comunidad de Madrid and TEC2009-14587-C03-02 by Spanish Government, Consejo Social of Universidad Politecnica de Madrid and fellowship RR02/2009 (UPM) have provided funds towards this project.

Disclosures

Ana Beatriz Solana Sánchez declares that she is employee of General Electric Global Research Center. However, this research work was carried out while doing her PhD in the Center for Biomedical Technology in Madrid under public funding sources detailed in the acknowledgements.

Kenia Martínez, Juan Antonio Hernández-Tamames, Victoria San Antonio-Arce, Rafael Toledano, Irene García-Morales, Juan Alvárez-Linera, Antonio Gil-Nágel and Francisco del Pozo declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Solana, A.B., Martínez, K., Hernández-Tamames, J.A. et al. Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy. Brain Imaging and Behavior 10, 373–386 (2016). https://doi.org/10.1007/s11682-015-9404-6

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