Brain Topography

, Volume 28, Issue 2, pp 305–317 | Cite as

Detecting Functional Hubs of Ictogenic Networks

  • Frederic ZublerEmail author
  • Heidemarie Gast
  • Eugenio Abela
  • Christian Rummel
  • Martinus Hauf
  • Roland Wiest
  • Claudio Pollo
  • Kaspar Schindler
Original Paper


Quantitative EEG (qEEG) has modified our understanding of epileptic seizures, shifting our view from the traditionally accepted hyper-synchrony paradigm toward more complex models based on re-organization of functional networks. However, qEEG measurements are so far rarely considered during the clinical decision-making process. To better understand the dynamics of intracranial EEG signals, we examine a functional network derived from the quantification of information flow between intracranial EEG signals. Using transfer entropy, we analyzed 198 seizures from 27 patients undergoing pre-surgical evaluation for pharmaco-resistant epilepsy. During each seizure we considered for each network the in-, out- and total “hubs”, defined respectively as the time and the EEG channels with the maximal incoming, outgoing or total (bidirectional) information flow. In the majority of cases we found that the hubs occur around the middle of seizures, and interestingly not at the beginning or end, where the most dramatic EEG signal changes are found by visual inspection. For the patients who then underwent surgery, good postoperative clinical outcome was on average associated with a higher percentage of out- or total-hubs located in the resected area (for out-hubs p = 0.01, for total-hubs p = 0.04). The location of in-hubs showed no clear predictive value. We conclude that the study of functional networks based on qEEG measurements may help to identify brain areas that are critical for seizure generation and are thus potential targets for focused therapeutic interventions.


Quantitative EEG Functional brain networks Epilepsy surgery Symbolic transfer entropy 

Supplementary material

10548_2014_370_MOESM1_ESM.pdf (177 kb)
Supplementary material 1 (PDF 176 kb)


  1. Bondallaz P, Box C, Rossetti AO, Foletti G, Spinelli L, Vulliemoz S, Seeck M, Pollo C (2012) Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy. Seizure 13:1059–1311Google Scholar
  2. Daw CS, Finney CEA, Tracy ER (2013) A review of symbolic analysis of experimental data. Rev Sci Instrum 74:915–930CrossRefGoogle Scholar
  3. Engel J, Thompson PM, Stern JM, Staba RJ, Bragin A, Mody I (2013) Connectomics and epilepsy. Curr Opin Neurol 26(2):186–194CrossRefPubMedCentralPubMedGoogle Scholar
  4. Granger CWJ (1969) Investigating causal relations by econometric models and cross-spectral methods. Econometrica 37(3):424–438CrossRefGoogle Scholar
  5. He B, Yang L, Wilke C, Yuan H (2011) Electrophysiological imaging of brain activity and connectivity-challenges and opportunities. IEEE Trans Biomed Eng 58(7):1918–31CrossRefPubMedCentralPubMedGoogle Scholar
  6. Jiruska P, de Curtis M, Jefferys JGR, Schevon CA, Schiff SJ, Schindler K (2013) Synchronization and desynchronization in epilepsy: controversies and hypotheses. J Physiol 591(4):787–97CrossRefPubMedCentralPubMedGoogle Scholar
  7. Kaiser A, Schreiber T (2002) Information transfer in continuous processes. Phys D 166(1):43–62CrossRefGoogle Scholar
  8. Kaminski MJ, Blinowska KJ (1991) A new method of the description of the information flow in the brain structures. Biol Cybern 65:203–210CrossRefPubMedGoogle Scholar
  9. Kramer MA, Eden UT, Kolaczyk ED, Zepeda R, Eskandar EN, Cash SS (2010) Coalescence and fragmentation of cortical networks during focal seizures. J Neurosci 30:10076–10085CrossRefPubMedCentralPubMedGoogle Scholar
  10. Kramer MA, Cash SS (2012) Epilepsy as a disorder of cortical network organization. Neuroscientist 18(4):360–372CrossRefPubMedCentralPubMedGoogle Scholar
  11. Kramer MA, Truccolo W, Eden UT, Lepage KQ, Hochberg LR, Eskandar EN, Madsen JR, Lee JW, Maheshwari A, Halgren E, Chu CJ, Cash SS (2012) Human seizures self-terminate across spatial scales via a critical transitino. Proc Natl Acad Sci 09(51):21116–21CrossRefGoogle Scholar
  12. Lemieux L, Daunizeau J, Walker MC (2011) Concepts of connectivity and human epileptic activity. Front Syst Neurosci 5:12CrossRefPubMedCentralPubMedGoogle Scholar
  13. Liu YY, Slotine JJ, Barabsi AL (2011) Controlability of complex networks. Nature 473:167–173CrossRefPubMedGoogle Scholar
  14. Lizier JT, Heinzle J, Horstmann A, Haynes JD, Prokopenko M (2011) Multivariate information-theoretic measures reveal directed information structure and task relevant changes in fMRI connectivity. J Comput Neurosci 30(1):85–107CrossRefPubMedGoogle Scholar
  15. Lu Y, Yang L, Worrell GA, He B (2012) Seizure source imaging by means of FINE spatio-temporal dipole localization and directed transfer function in partial epilepsy patients. Clin Neurophysiol 123(7):1275–1283CrossRefPubMedCentralPubMedGoogle Scholar
  16. Marschinski R, Kantz H (2002) Analysing the information flow between financial time series. Eur Phys J B 3(2):275–281CrossRefGoogle Scholar
  17. Nichols TE, Holmes AP (2001) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25CrossRefGoogle Scholar
  18. Penfield W, Jasper H (1954) Epilepsy and the functional anatomy of the human brain. Little Brown, BostonGoogle Scholar
  19. Rorden C, Bonilha L, Fridriksson J, Bender B, Karnath HO (2012) Age-specific CT and MRI templates for spatial normalization. Neuroimage 61(4):957–965CrossRefPubMedCentralPubMedGoogle Scholar
  20. Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52(3):1059–1069CrossRefPubMedGoogle Scholar
  21. Rummel C, Abela E, Hauf M, Wiest R, Schindler K (2013) Ordinal patterns in epileptic brains: analysis of intracranial EEG and simultaneous EEG-fMRI. Eur Phys J Spec Top 222:569–585CrossRefGoogle Scholar
  22. Schindler K, Leung H, Elger CE, Lehnertz K (2007) Assessing seizure dynamics by analyzing the correlation structure of multichannel intracranial EEG. Brain 130:65–77CrossRefPubMedGoogle Scholar
  23. Schindler K, Bialonski S, Horstmann MT, Elger CE, Lehnertz K (2008) Evolving functional network properties and synchronizability during human epileptic seizures. Chaos 18:033119CrossRefPubMedGoogle Scholar
  24. Schindler K, Gast H, Stieglitz L, Stibal A, Hauf M, Wiest R, Mariani L, Rummel C (2011) Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures. Epilepsia 52(10):1771–1780CrossRefPubMedGoogle Scholar
  25. Schindler K, Gast H, Goodfellow M, Rummel C (2012) On seeing the trees and the forest: single-signal and multisignal analysis of periictal intracranial EEG. Epilepsia 53(9):1658–1668CrossRefPubMedGoogle Scholar
  26. Schreiber T (2000) Measuring information transfer. Phys Rev Lett 85:461–464CrossRefPubMedGoogle Scholar
  27. Stam CJ, van Straaten ECW (2012) The organization of physiological brain networks. Clin Neurophysiol 123(6):1067–1087CrossRefPubMedGoogle Scholar
  28. Staniek M, Lehnertz K (2008) Symbolic transfer entropy. Phys Rev Lett 100(15):158101CrossRefPubMedGoogle Scholar
  29. Staniek M, Lehnertz K (2009) Symbolic transfer entropy: inferring directionality in biosignals. Biomed Tech 54(6):323–328CrossRefGoogle Scholar
  30. Truccolo W, Donoghue JA, Hochberg LR, Eskandar EN, Madsen JR, Anderson WS, Brown EN, Halgren E, Cash SS (2011) Single-neuron dynamics in human focal epilepsy. Nat Neurosc 14:635–641CrossRefGoogle Scholar
  31. van Diessen E, Diederen SJH, Braun KPJ, Jansen FE, Stam CJ (2013) Functional and structural brain networks in epilepsy: what have we learned? Epilepsia 54(11):1855–1865CrossRefPubMedGoogle Scholar
  32. Warren CP, Hu S, Stead M, Brinkmann BH, Bower MR, Worrell GA (2010) Synchrony in normal and focal epileptic brain: the seizure onset zone is functionally disconnected. J Neurophysiol 104(6):3530–3539CrossRefPubMedCentralPubMedGoogle Scholar
  33. Wilke C, Ding L, He B (2008) Estimation of time-varying connectivity patterns through the use of an adaptive directed transfer function. IEEE Trans Biomed Eng 55(11):2557–2564CrossRefPubMedCentralPubMedGoogle Scholar
  34. Wilke C, Worrell G, He B (2011) Graph analysis of epileptogenic networks in human partial epilepsy. Epilepsia 52(1):84–93CrossRefPubMedCentralPubMedGoogle Scholar
  35. Zanin M, Zunino L, Rosso OA, Papo D (2012) Permutation entropy and its main biomedical and econophysics applications: a review. Entropy 14(8):1553–1577CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Frederic Zubler
    • 1
    Email author
  • Heidemarie Gast
    • 1
  • Eugenio Abela
    • 2
  • Christian Rummel
    • 2
  • Martinus Hauf
    • 2
  • Roland Wiest
    • 2
  • Claudio Pollo
    • 3
  • Kaspar Schindler
    • 1
  1. 1.Department of Neurology, Inselspital Bern, Bern University HospitalUniversity of BernBernSwitzerland
  2. 2.Support center for advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern, Bern University HospitalUniversity of BernBernSwitzerland
  3. 3.Department of Neurosurgery, Inselspital Bern, Bern University HospitalUniversity of BernBernSwitzerland

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