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A Systems-Level Approach to Human Epileptic Seizures

Neuroinformatics volume 11, pages 159–173 (2013)Cite this article

Abstract

Epileptic seizures are due to the pathological collective activity of large cellular assemblies. A better understanding of this collective activity is integral to the development of novel diagnostic and therapeutic procedures. In contrast to reductionist analyses, which focus solely on small-scale characteristics of ictogenesis, here we follow a systems-level approach, which combines both small-scale and larger-scale analyses. Peri-ictal dynamics of epileptic networks are assessed by studying correlation within and between different spatial scales of intracranial electroencephalographic recordings (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant epilepsy. Epileptiform activity as recorded by a single iEEG electrode is determined objectively by the signal derivative and then subjected to a multivariate analysis of correlation between all iEEG channels. We find that during seizure, synchrony increases on the smallest and largest spatial scales probed by iEEG. In addition, a dynamic reorganization of spatial correlation is observed on intermediate scales, which persists after seizure termination. It is proposed that this reorganization may indicate a balancing mechanism that decreases high local correlation. Our findings are consistent with the hypothesis that during epileptic seizures hypercorrelated and therefore functionally segregated brain areas are re-integrated into more collective brain dynamics. In addition, except for a special sub-group, a highly significant association is found between the location of ictal iEEG activity and the location of areas of relative decrease of localised EEG correlation. The latter could serve as a clinically important quantitative marker of the seizure onset zone (SOZ).

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Abbreviations

CC:

equal-time cross-correlation

EEG:

electroencephalogram

FLE:

frontal lobe epilepsy

Fo:

foramen ovale

iEEG:

intracranial electroencephalogram

MRI:

magnetic resonance imaging

PLE:

parietal lobe epilepsy

TCS:

total correlation strength

TLE:

temporal lobe epilepsy

SCC:

slope cross-correlation

SOZ:

seizure onset zone

References

  • Alarcon, G., Binnie, C., Elwes, R., & Polkey, C. (1995). Power spectrum and intracranial EEG patterns at seizure onset in partial epilepsy. Electroencephalography and Clinical Neurophysiology, 94, 326–337.

    PubMed  Article  CAS  Google Scholar 

  • Allen, P., Fish, D., & Smith, S. (1992). Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy. Electroencephalography and Clinical Neurophysiology, 82, 155–159.

    PubMed  Article  CAS  Google Scholar 

  • Bartolomei, F., Wendling, F., Bellanger, J. J., Reis, J., & Patrick, C. (2001). Neural networks involving the medial temporal structures in temporal lobe epilepsy. Clinical Neurophysiology, 112, 1746–1760.

    PubMed  Article  CAS  Google Scholar 

  • Blumenfeld, H., McNally, K. A., Vanderhill, S. D., Paige, A. L., Chung, R., Davis, K., Norden, A. D., Stokking, R., Studholme, C., Novotny, E. J., Zubal, I. G., & Spencer, S. S. (2004). Positive and negative network correlations in temporal lobe epilepsy. Cerebral Cortex, 14, 892–902.

    PubMed  Article  Google Scholar 

  • Blumenfeld, H., Varghese, G. I., Purcaro, M. J., Motelow, J. E., Enev, M., McNally, K. A., Levin, A. R., Hirsch, L. J., Tikofsky, R., Zubal, I. G., Paige, A. L., & Spencer, S. S. (2009). Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures. Brain, 132, 999–1012.

    PubMed  Article  CAS  Google Scholar 

  • Breakspear, M. (2004). “Dynamic” connectivity in neural systems. Theoretical and empirical considerations. Neuroinformatics, 2, 205–224.

    PubMed  Article  Google Scholar 

  • Breakspear, M., Roberts, J. A., Terry, J. R., Rodrigues, S., & Robinson, P. A. (2006). A unifying explanation of generalized seizures via the bifurcation analysis of a dynamical brain model. Cerebral Cortex, 16, 1296–1313.

    PubMed  Article  CAS  Google Scholar 

  • Bressler, S., & Kelso, J. (2001). Cortical coordination dynamics and cognition. Trends in Cognitive Science, 5, 26–36.

    Article  Google Scholar 

  • Dauwels, J., Eskandar, E., & Cash, S. (2009). Localization of seizure onset area from intracranial non-seizure EEG by exploiting locally enhanced synchrony. Conference Proceedings IEEE Engineering in Medicine Biology and Society, 2009, 2180–2183.

    Google Scholar 

  • David, O., Blauwblomme, T., Job, A.-S., Chabardés, S., Hoffmann, D., Minotti, L., & Kahane, P. (2011). Imaging the seizure onset zone with stereo-electroencephalography. Brain, 134, 2898–2911.

    PubMed  Article  Google Scholar 

  • de Boer, H. M., Mula, M., & Sander, J. W. (2008). The global burden and stigma of epilepsy. Epilepsy & Behavior, 12, 540–546.

    Article  Google Scholar 

  • de Curtis, M., & Gnatkovsky, V. (2009). Reevaluating the mechanisms of focal ictogenesis: the role of low-voltage fast activity. Epilepsia, 50, 2514–2525.

    PubMed  Article  Google Scholar 

  • Elger, C. E., & Schmidt, D. (2008). Modern treatment of epilepsy: a practical approach. Epilepsy & Behavior, 12, 501–539.

    Article  Google Scholar 

  • Feldt, S., Osterhage, H., Mormann, F., Lehnertz, K., & Zochowski, M. (2007). Internetwork and intranetwork communications during bursting dynamics: Applications to seizure prediction. Physical Review E, 76, 021920.

    Article  CAS  Google Scholar 

  • Fisher, R., Webber, W., Lesser, R., Arroya, S., & Uematsu, S. (1992). High-frequency EEG activity at the start of seizures. Journal of Clinical Neurophysiology, 9, 441–448.

    PubMed  Article  CAS  Google Scholar 

  • Frei, M. G., Zaveri, H. P., Arthurs, S., Bergey, G. K., Jouny, C. C., Lehnertz, K., Gotman, J., Osorio, I., Netoff, T. I., Freeman, W. J., Jefferys, J., Worrell, G., Le Van Quyen, M., Schiff, S. J., & Mormann, F. (2010). Controversies in epilepsy: Debates held during the fourth international workshop on seizure prediction. Epilepsy & Behavior, 19, 4–16.

    Article  Google Scholar 

  • Friston, K. J., Tononi, G., Sporns, O., & Edelman, G. M. (1995). Characterizing the complexity of neuronal interactions. Human Brain Mapping, 3, 302–314.

    Article  Google Scholar 

  • Galderisi, S., & Sannita, W. G. (2006). Pharmaco-EEG: a history of progress and a missed opportunity. Clinical EEG and Neuroscience, 37, 61–65.

    PubMed  Article  Google Scholar 

  • Goodfellow, M., Schindler, K., & Baier, G. (2011). Intermittent spike–wave dynamics in a heterogeneous, spatially extended neural mass model. NeuroImage, 55, 920–932.

    PubMed  Article  Google Scholar 

  • Goodfellow, M., Schindler, K., & Baier, G. (2012). Self-organised transients in a neural mass model of epileptogenic tissue dynamics. NeuroImage, 59, 2644–2660.

    PubMed  Article  Google Scholar 

  • Guye, M., Reis, J., Tamura, M., Wendling, F., Mc Gonigal, A., Patrick, C., & Bartolomei, F. (2006). The role of corticothalamic coupling in human temporal lobe epilepsy. Brain, 129, 1917–1928.

    PubMed  Article  Google Scholar 

  • Herrnstein, R. J. (1979). Acquisition, generalization, and discrimination reversal of a natural concept. Journal of Experimental Psychology: Animal Behavior Processes, 5, 116–129.

    PubMed  Article  CAS  Google Scholar 

  • Herrnstein, R. J., Loveland, D. H., & Cable, C. (1976). Natural concepts in pigeons. Journal of Experimental Psychology: Animal Behavior Processes, 2, 285–302.

    Article  Google Scholar 

  • Iasemidis, L. D., Shiau, D. S., Sackellares, J. C., Pardalos, P. M., & Prasad, A. (2004). Dynamical resetting of the human brain at epileptic seizures: Application of nonlinear dynamics and global optimization techniques. IEEE Transactions on Biomedical Engineering, 51, 493–506.

    PubMed  Article  Google Scholar 

  • Jacobs, J., LeVan, P., Chatillon, C. E., Olivier, A., Dubeau, F., & Gotman, J. (2009). High frequency oscillations in intracranial eegs mark epileptogenicity rather than lesion type. Brain, 132, 1022–1037.

    PubMed  Article  Google Scholar 

  • Kramer, M.A., Cash, S.S. (2012). Epilepsy as a disorder of cortical network organization, Neuroscientist, 18(4):360–372.

    Google Scholar 

  • Kramer, M. A., Eden, U. T., Kolaczyk, E. D., Zepeda, R., Eskandar, E. N., & Cash, S. S. (2010). Coalescence and fragmentation of cortical networks during focal seizures. Journal of Neuroscience, 30, 10076–10085.

    PubMed  Article  CAS  Google Scholar 

  • Lennox, W. (1941). The causes of seizures. Science and seizures (pp. 63–73). New York: Harper.

    Google Scholar 

  • Lin, K., & Benbadis, S. R. (2009). Death and epilepsy. Expert Review of Neurotherapeutics, 9, 781–783.

    PubMed  Article  Google Scholar 

  • Liu, Z. (2004). Measuring the degree of synchronization from time series data. Europhysics Letters, 68, 19–25.

    Article  CAS  Google Scholar 

  • Lüders, H. O. (2008). Textbook of Epilepsy Surgery. London: Informa Healthcare.

    Book  Google Scholar 

  • Lytton, W. (2008). Computer modelling of epilepsy. Nature Reviews Neuroscience, 9(8), 626–637.

    PubMed  Article  CAS  Google Scholar 

  • McCormick, D. A., & Contreras, D. (2001). On the cellular and network bases of epileptic seizures. Annual Review of Physiology, 63, 815–846.

    PubMed  Article  CAS  Google Scholar 

  • Majumdar, K. K., & Vardhan, P. (2011). Automatic seizure detection in ECoG by differential operator and windowed variance. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 19, 356–365.

    PubMed  Article  Google Scholar 

  • Mormann, F., Andrzejak, R. G., Kreuz, T., Rieke, C., David, P., Elger, C. E., & Lehnertz, K. (2003). Automated detection of a preseizure state based on a decrease in synchronization in intracranial electroencephalogram recordings from epilepsy patients. Physical Review E, 67, 021912.

    Article  Google Scholar 

  • Mormann, F., Kreuz, T., Andrzejak, R. G., David, P., Lehnertz, K., & Elger, C. E. (2003). Epileptic seizures are preceded by a decrease in synchronization. Epilepsy Research, 53, 173–185.

    PubMed  Article  Google Scholar 

  • Müller, M., Baier, G., Galka, A., Stephani, U., & Muhle, H. (2005). Detection and characterization of changes of correlation structure in multivariate time series. Physical Review E, 71, 046116.

    Article  Google Scholar 

  • Müller, M., Baier, G., Rummel, C., & Schindler, K. (2008). Estimating the strength of genuine and random correlations in non-stationary multivariate time series. Europhysics Letters, 84, 10009.

    Article  Google Scholar 

  • Niederhauser, J. J., Esteller, R., Echauz, J., Vachtsevanos, G., & Litt, B. (2003). Detection of seizure precursors from depth-EEG using a sign periodogram transform. IEEE Transactions on Biomedical Engineering, 50, 449–458.

    PubMed  Article  Google Scholar 

  • Penfield, W., & Jasper, H. (1954). Hypersynchrony. Epilepsy and the functional anatomy of the human brain. Boston: Little, Brown and Company.

    Google Scholar 

  • Plerou, V., Gopikrishnan, P., Rosenow, B., Nunes Amaral, L. A., Guhr, T., & Stanley, H. E. (2002). Random matrix approach to cross correlations in financial data. Physical Review E, 65, 066126.

    Article  Google Scholar 

  • Rosenow, F., & Lüders, H. (2001). Presurgical evaluation of epilepsy. Brain, 124, 1683–1700.

    PubMed  Article  CAS  Google Scholar 

  • Rummel, C., Müller, M., & Schindler, K. (2008). Data-driven estimates of the number of clusters in multivariate time series. Physical Review E, 78, 066703.

    Article  Google Scholar 

  • Schevon, C., Cappell, J., Emerson, R., Isler, J., Grieve, P., Goodman, R., Mckhann, G., Jr., Weiner, H., Doyle, W., Kuzniecky, R., Devinsky, O., & Gillam, F. (2007). Cortical abnormalities in epilepsy revealed by local eeg synchrony. NeuroImage, 35, 140–148.

    PubMed  Article  CAS  Google Scholar 

  • Schiff, S., Colella, D., Jacyna, G. M., Hughes, E., Creekmore, J., Marshall, A., Bozek-Kuzmicki, M., Benke, G., Gaillard, W., Conry, J., & Weinstein, S. (2000). Brain chirps: spectrographic signatures of epileptic seizures. Clinical Neurophysiology, 111, 953–958.

    PubMed  Article  CAS  Google Scholar 

  • Schiff, S. J., Sauer, T., Kumar, R., & Weinstein, S. L. (2005). Neuronal spatiotemporal pattern discrimination: The dynamical evolution of seizures. NeuroImage, 28, 1043–1055.

    PubMed  Article  Google Scholar 

  • Schindler, K., Amor, F., Gast, H., Müller, M., Stibal, A., Mariani, L., & Rummel, C. (2010). Peri-ictal correlation dynamics of high frequency (80–200 Hz) intracranial EEG. Epilepsy Research, 89, 72–81.

    PubMed  Article  Google Scholar 

  • Schindler, K., Elger, C. E., & Lehnertz, K. (2007). Increasing synchronization may promote seizure termination: Evidence from status epilepticus. Clinical Neurophysiology, 118, 1955–1968.

    PubMed  Article  Google Scholar 

  • Schindler, K., Gast, H., Goodfellow, M., Rummel, C. (2012). On seeing the trees and the forest: Single-signal and multisignal analysis of peri-ictal intracranial EEG. Epilepsia. doi:10.1111/j.1528-1167.2012.03588.x.

  • Schindler, K., Leung, H., Elger, C. E., & Lehnertz, K. (2007). Assessing seizure dynamics by analysing the correlation structure of multichannel intracranial EEG. Brain, 130, 65–77.

    PubMed  Article  Google Scholar 

  • Schindler, K., Wiest, R., Kollar, M., & Donati, F. (2001). Using simulated neuronal cell models for detection of epileptic seizures in foramen ovale and scalp EEG. Clinical Neurophysiology, 112, 1006–1017.

    PubMed  Article  CAS  Google Scholar 

  • Schreiber, T., & Schmitz, A. (2000). Surrogate time series. Physica D, 142, 346–382.

    Article  Google Scholar 

  • Siegel, S. (1956). Non-parametric Statistics for the Behavioral Sciences. New York: McGraw-Hill.

    Google Scholar 

  • Silberstein, R. B. (1995). Neuromodulation of neocortical dynamics. In P. L. Nunez (Ed.), Neocortical dynamics and human EEG rhythms (pp. 591–627). New York: Oxford University Press.

    Google Scholar 

  • Smith, G., Ferguson, P. L., Saunders, L. L., Wagner, J. L., Wannamaker, B. B., & Selassie, A. W. (2009). Psychosocial factors associated with stigma in adults with epilepsy. Epilepsy & Behavior, 16, 484–490.

    Article  Google Scholar 

  • Spencer, S. S. (2002). Neural networks in human epilepsy: Evidence of and implications for treatment. Epilepsia, 43, 219–227.

    PubMed  Article  Google Scholar 

  • Stam, C.J., Reijneveld, J.C. (2007). Graph theoretical analysis of complex networks in the brain. Nonlinear Biomedical Physics, 1(1), 3.

    Google Scholar 

  • Takigawa, M., Fukuzako, H., Ueyama, K., Takeuchi, K., Fukuzako, T., & Nomaguchi, M. (1994). Developing of EEG print and its preliminary technical application. Japan Journal of Psychiatry Neurology, 48, 91–97.

    CAS  Google Scholar 

  • Tononi, G., Sporns, O., & Edelman, G. M. (1994). A measure for brain complexity: Relating functional segregation and integration in the nervous system. Proceedings of the National Academy of Sciences, 91, 5033–5037.

    Article  CAS  Google Scholar 

  • Uhlhaas, P. J., & Singer, W. (2006). Neural synchrony in brain disorders: Relevance for cognitive dysfunctions and pathophysiology. Neuron, 52, 155–168.

    PubMed  Article  CAS  Google Scholar 

  • Utsugi, A., Ino, K., & Oshikawa, M. (2004). Random matrix theory analysis of cross correlations in financial markets. Physical Review E, 70, 026110.

    Article  Google Scholar 

  • Varela, F., Lachaux, J. P., Rodriguez, E., & Martinerie, J. (2001). The brainweb: Synchronization and large-scale integration. Nature Review Neuroscience, 2, 229–239.

    Article  CAS  Google Scholar 

  • Warren, C. P., Hu, S., Stead, M., Brinkmann, B. H., Bower, M. R., & Worrell, G. A. (2010). Synchrony in Normal and Focal Epileptic Brain: The Seizure Onset Zone is Functionally Disconnected. Journal of Neurophysiology, 104, 3530–3539.

    PubMed  Article  Google Scholar 

  • Weder, B. J., Schindler, K., Loher, T. J., Wiest, R., Wissmeyer, M., Ritter, P., Lovblad, K., Donati, F., & Missimer, J. (2006). Brain areas involved in medial temporal lobe seizures: a principal component analysis of ictal spect data. Human Brain Mapping, 27, 520–534.

    PubMed  Article  Google Scholar 

  • Wendling, F., Bartolomei, F., Bellanger, J., Bourien, J., & Chauvel, P. (2003). Epileptic fast intracerebral activity for spatial decorrelation at seizure onset. Brain, 126, 1449–1459.

    PubMed  Article  CAS  Google Scholar 

  • Wendling, F., Bartolomei, F., Bellanger, J., & Chauvel, P. (2002). Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition. European Journal of Neuroscience, 15, 1499–1508.

    PubMed  Article  CAS  Google Scholar 

  • Wessel, N., Suhrbier, A., Riedl, M., Marwan, N., Malberg, H., Bretthauer, G., Penzel, T., & Kurths, J. (2009). Detection of time-delayed interactions in biosignals using symbolic coupling traces. Europhysics Letters, 87, 10004.

    Article  Google Scholar 

  • Worrell, G. A., Gardner, A. B., Stead, S. M., Hu, S., Goerss, S., Cascino, G. J., Meyer, F. B., Marsh, R., & Litt, B. (2008). High-frequency oscillations in human temporal lobe: simultaneous microwire and clinical macroelectrode recordings. Brain, 131, 928–937.

    PubMed  Article  Google Scholar 

  • Worrell, G. A., Parish, L., Cranstoun, S. D., Jonas, R., Baltuch, G., & Litt, B. (2004). High-frequency oscillations and seizure generation in neocortical epilepsy. Brain, 127, 1496–1506.

    PubMed  Article  Google Scholar 

  • Zachry, W. M., III, Doan, Q. D., Smith, B. J., Clewell, J. D., & Griffith, J. M. (2009). Direct medical costs for patients seeking emergency care for losses of epilepsy control in a U.S. managed care setting. Epilepsy & Behavior, 16, 268–273.

    Article  Google Scholar 

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Acknowledgments

C.R. and K.S. thank Markus Müller for fruitful discussions. This work was supported by Deutsche Forschungsgemeinschaft, Germany (grant RU 1401/2-1) and Schweizerischer Nationalfonds, Switzerland (projects 320030-122010 and 33CM30-124089). M.G. acknowledges financial support from the EPSRC and BBSRC (UK).

Conflicts of Interest

None of the authors has any conflict of interest to disclose.

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Affiliations

  1. Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland

    Christian Rummel, Martinus Hauf & Roland Wiest

  2. Systems Biology Doctoral Training Centre, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK

    Marc Goodfellow

  3. Centre for Interdisciplinary Computational and Dynamical Analysis (CICADA), School of Mathematics, The University of Manchester, Manchester, UK

    Marc Goodfellow

  4. qEEG group, Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

    Heidemarie Gast, Frédérique Amor & Kaspar Schindler

  5. Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Alexander Stibal

  6. Department of Neurosurgery, Basel University Hospital, University of Basel, Basel, Switzerland

    Luigi Mariani

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  1. Christian Rummel
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  2. Marc Goodfellow
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Correspondence to Christian Rummel.

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Rummel, C., Goodfellow, M., Gast, H. et al. A Systems-Level Approach to Human Epileptic Seizures. Neuroinform 11, 159–173 (2013). https://doi.org/10.1007/s12021-012-9161-2

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Keywords

  • Epileptic focal onset seizures
  • Quantitative EEG
  • High frequency oscillations
  • Pre-surgical evaluation
  • Seizure onset zone