Brain Topography

, Volume 27, Issue 5, pp 683–704 | Cite as

Scalp EEG is not a Blur: It Can See High Frequency Oscillations Although Their Generators are Small

  • R. ZelmannEmail author
  • J. M. Lina
  • A. Schulze-Bonhage
  • J. Gotman
  • J. Jacobs
Original Paper


High frequency oscillations (HFOs) are emerging as biomarkers of epileptogenicity. They have been shown to originate from small brain regions. Surprisingly, spontaneous HFOs can be recorded from the scalp. To understand how is it possible to observe these small events on the scalp, one avenue is the analysis of the cortical correlates at the time of scalp HFOs. Using simultaneous scalp and intracranial recordings of 11 patients, we studied the spatial distribution of scalp events on the cortical surface. For typical interictal epileptiform discharges the subdural distributions were, as expected, spatially extended. On the contrary, for scalp HFOs the subdural maps corresponded to focal sources, consisting of one or a few small spatial extent activations. These topographies suggest that small cortical areas generated the HFOs seen on the scalp. Similar scalp distributions corresponded to distinct distributions on a standard 1 cm subdural grid and averaging similar scalp HFOs resulted in focal subdural maps. The assumption that a subdural grid “sees” everything that contributes to the potential of nearby scalp contacts was not valid for HFOs. The results suggest that these small extent events are spatially undersampled with standard scalp and grid inter-electrode distances. High-density scalp electrode distributions seem necessary to obtain a solid sampling of HFOs on the scalp. A better understanding of the influence of spatial sampling on the observation of high frequency brain activity on the scalp is important for their clinical use as biomarkers of epilepsy.


High frequency oscillations Scalp HFO Ripple Simultaneous scalp and subdural EEG Spatial sampling 



We thank Dr. Federico Melani for his help in the identification of interictal epileptiform discharges. We thank Francois Tadel and Dr. Sylvain Baillet for their suggestions on how to implement brainstorm for our simulations. We are grateful to Dr. Matthias Dümpelmann for his help in obtaining the data. This project was founded in part by DAAD short-term scholarship, the Savoy Foundation, and grant MOP-102,710 from the Canadian Institutes of Health Research. JJ was supported by the German Research Foundation (grant JA 1,725/2-1).

Supplementary material

10548_2013_321_MOESM1_ESM.doc (46 kb)
Supplementary material 1 (DOC 46 kb)


  1. Alarcon G, Guy CN, Binnie CD, Walker SR, Elwes RD, Polkey CE (1994) Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation. J Neurol Neurosurg Psychiatry 57(4):435–449PubMedCentralPubMedCrossRefGoogle Scholar
  2. Andrade-Valença LP, Dubeau F, Mari F, Zelmann R, Gotman J (2011) Interictal scalp fast oscillations as a marker of the seizure onset zone. Neurology 77(6):524–531. doi: 10.1212/WNL.0b013e318228bee2 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bagshaw AP, Jacobs J, LeVan P, Dubeau F, Gotman J (2009) Effect of sleep stage on interictal high-frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy. Epilepsia 50(4):617–628PubMedCentralPubMedCrossRefGoogle Scholar
  4. Ball T, Demandt E, Mutschler I, Neitzel E, Mehring C, Vogt K, Aertsen A, Schulze-Bonhage A (2008) Movement related activity in the high gamma range of the human EEG. Neuroimage 41(2):302–310PubMedCrossRefGoogle Scholar
  5. Bénar CG, Chauviere L, Bartolomei F, Wendling F (2010) Pitfalls of high-pass filtering for detecting epileptic oscillations: a technical note on “false” ripples. Clin Neurophysiol 121(3):301–310PubMedCrossRefGoogle Scholar
  6. Bénar CG, Gotman J (2002) Modeling of post-surgical brain and skull defects in the EEG inverse problem with the boundary element method. Clin Neurophysiol 113(1):48–56PubMedCrossRefGoogle Scholar
  7. Boonyapisit K, Najm I, Klem G, Ying Z, Burrier C, LaPresto E, Nair D, Bingaman W, Prayson R, Luders H (2003) Epileptogenicity of focal malformations due to abnormal cortical development: direct electrocorticographic-histopathologic correlations. Epilepsia 44(1):69–76PubMedCrossRefGoogle Scholar
  8. Bragin A, Mody I, Wilson CL, Engel J Jr (2002) Local generation of fast ripples in epileptic brain. J Neurosci 22(5):2012–2021PubMedGoogle Scholar
  9. Brodbeck V, Spinelli L, Lascano AM, Wissmeier M, Vargas MI, Vulliemoz S, Pollo C, Schaller K, Michel CM, Seeck M (2011) Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients. Brain 134(Pt 10):2887–2897. doi: 10.1093/brain/awr243 PubMedCentralPubMedCrossRefGoogle Scholar
  10. Buzsáki G, Draguhn A (2004) Neuronal oscillations in cortical networks. Science 304(5679):1926–1929. doi: 10.1126/science.1099745 PubMedCrossRefGoogle Scholar
  11. Chrobak JJ, Buzsaki G (1996) High-frequency oscillations in the output networks of the hippocampal–entorhinal axis of the freely behaving rat. J Neurosci 16(9):3056–3066PubMedGoogle Scholar
  12. Cooper R, Winter AL, Crow HJ, Walter WG (1965) Comparison of subcortical, cortical and scalp activity using chronically indwelling electrodes in man. Electroencephalogr Clin Neurophysiol 18:217–228PubMedCrossRefGoogle Scholar
  13. Cosandier-Rimele D, Merlet I, Badier JM, Chauvel P, Wendling F (2008) The neuronal sources of EEG: modeling of simultaneous scalp and intracerebral recordings in epilepsy. Neuroimage 42(1):135–146. doi: 10.1016/j.neuroimage.2008.04.185 PubMedCrossRefGoogle Scholar
  14. Crepon B, Navarro V, Hasboun D, Clemenceau S, Martinerie J, Baulac M, Adam C, Le Van Quyen M (2010) Mapping interictal oscillations greater than 200 Hz recorded with intracranial macroelectrodes in human epilepsy. Brain 133(Pt 1):33–45. doi: 10.1093/brain/awp277 PubMedCrossRefGoogle Scholar
  15. Curio G (2000) Linking 600-Hz “spikelike” EEG/MEG wavelets (“sigma-bursts”) to cellular substrates: concepts and caveats. J Clin Neurophysiol 17(4):377–396PubMedCrossRefGoogle Scholar
  16. Duun-Henriksen J, Kjaer TW, Madsen RE, Jespersen B, Duun-Henriksen AK, Remvig LS, Thomsen CE, Sorensen HB (2013) Subdural to subgaleal EEG signal transmission: the role of distance, leakage and insulating affectors. Clin Neurophysiol. doi: 10.1016/j.clinph.2013.02.112 PubMedGoogle Scholar
  17. Freeman WJ, Rogers LJ, Holmes MD, Silbergeld DL (2000) Spatial spectral analysis of human electrocorticograms including the alpha and gamma bands. J Neurosci Methods 95(2):111–121PubMedCrossRefGoogle Scholar
  18. Gambardella A, Palmini A, Andermann F, Dubeau F, Da Costa JC, Quesney LF, Andermann E, Olivier A (1996) Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy. Electroencephalogr Clin Neurophysiol 98(4):243–249PubMedCrossRefGoogle Scholar
  19. Gloor P (1985) Neuronal generators and the problem of localization in electroencephalography: application of volume conductor theory to electroencephalography. J Clin Neurophysiol 2(4):327–354PubMedCrossRefGoogle Scholar
  20. Goncalves SI, de Munck JC, Verbunt JP, Bijma F, Heethaar RM, Lopes da Silva FH (2003) In vivo measurement of the brain and skull resistivities using an EIT-based method and realistic models for the head. IEEE Trans Biomed Eng 50(6):754–767PubMedCrossRefGoogle Scholar
  21. Gramfort A, Papadopoulo T, Olivi E, Clerc M (2010) OpenMEEG: opensource software for quasistatic bioelectromagnetics. Biomed Eng Online 9:45. doi: 10.1186/1475-925X-9-45 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Grenier F, Timofeev I, Steriade M (2001) Focal synchronization of ripples (80–200 Hz) in neocortex and their neuronal correlates. J Neurophysiol 86(4):1884–1898PubMedGoogle Scholar
  23. Hashiguchi K, Morioka T, Yoshida F, Miyagi Y, Nagata S, Sakata A, Sasaki T (2007) Correlation between scalp-recorded electroencephalographic and electrocorticographic activities during ictal period. Seizure 16(3):238–247. doi: 10.1016/j.seizure.2006.12.010 PubMedCrossRefGoogle Scholar
  24. Heasman BC, Valentin A, Alarcon G, Garcia Seoane JJ, Binnie CD, Guy CN (2002) A hole in the skull distorts substantially the distribution of extracranial electrical fields in an in vitro model. J Clin Neurophysiol 19(2):163–171PubMedCrossRefGoogle Scholar
  25. Holmes CJ, Hoge R, Collins L, Woods R, Toga AW, Evans AC (1998) Enhancement of MR images using registration for signal averaging. J Comput Assist Tomogr 22(2):324–333PubMedCrossRefGoogle Scholar
  26. Jacobs J, Levan P, Chatillon CE, Olivier A, Dubeau F, Gotman J (2009) High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type. Brain 132(Pt 4):1022–1037PubMedCentralPubMedGoogle Scholar
  27. Jacobs J, Staba R, Asano E, Otsubo H, Wu JY, Zijlmans M, Mohamed I, Kahane P, Dubeau F, Navarro V, Gotman J (2012) High-frequency oscillations (HFOs) in clinical epilepsy. Prog Neurobiol. doi: 10.1016/j.pneurobio.2012.03.001 PubMedCentralPubMedGoogle Scholar
  28. Jirsch JD, Urrestarazu E, LeVan P, Olivier A, Dubeau F, Gotman J (2006) High-frequency oscillations during human focal seizures. Brain 129(Pt 6):1593–1608PubMedCrossRefGoogle Scholar
  29. Kobayashi K, Oka M, Akiyama T, Inoue T, Abiru K, Ogino T, Yoshinaga H, Ohtsuka Y, Oka E (2004) Very fast rhythmic activity on scalp EEG associated with epileptic spasms. Epilepsia 45(5):488–496. doi: 10.1111/j.0013-9580.2004.45703.x PubMedCrossRefGoogle Scholar
  30. Kobayashi K, Watanabe Y, Inoue T, Oka M, Yoshinaga H, Ohtsuka Y (2010) Scalp-recorded high-frequency oscillations in childhood sleep-induced electrical status epilepticus. Epilepsia 51(10):2190–2194. doi: 10.1111/j.1528-1167.2010.02565.x PubMedCrossRefGoogle Scholar
  31. Kobayashi K, Yoshinaga H, Ohtsuka Y, Gotman J (2005) Dipole modeling of epileptic spikes can be accurate or misleading. Epilepsia 46(3):397–408. doi: 10.1111/j.0013-9580.2005.31404.x PubMedCrossRefGoogle Scholar
  32. Kybic J, Clerc M, Abboud T, Faugeras O, Keriven R, Papadopoulo T (2005) A common formalism for the integral formulations of the forward EEG problem. IEEE Trans Med Imaging 24(1):12–28PubMedCrossRefGoogle Scholar
  33. Lachaux JP, Rodriguez E, Martinerie J, Varela FJ (1999) Measuring phase synchrony in brain signals. Hum Brain Mapp 8(4):194–208PubMedCrossRefGoogle Scholar
  34. Lai Y, van Drongelen W, Ding L, Hecox KE, Towle VL, Frim DM, He B (2005) Estimation of in vivo human brain-to-skull conductivity ratio from simultaneous extra- and intra-cranial electrical potential recordings. Clin Neurophysiol 116(2):456–465. doi: 10.1016/j.clinph.2004.08.017 PubMedCrossRefGoogle Scholar
  35. Lanfer B, Roer C, Scherg M, Rampp S, Kellinghaus C, Wolters C (2013) Influence of a silastic ECoG grid on EEG/ECoG based source analysis. Brain Topogr 26(2):212–228. doi: 10.1007/s10548-012-0251-0 PubMedCrossRefGoogle Scholar
  36. Lantz G, Grave De Peralta R, Spinelli L, Seeck M, Michel CM (2003) Epileptic source localization with high density EEG: how many electrodes are needed? Clin Neurophysiol 114(1):63–69PubMedCrossRefGoogle Scholar
  37. Law SK (1993) Thickness and resistivity variations over the upper surface of the human skull. Brain Topogr 6:99–109PubMedCrossRefGoogle Scholar
  38. 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):1275–1283. doi: 10.1016/j.clinph.2011.11.007 PubMedCentralPubMedCrossRefGoogle Scholar
  39. Mégevand P, Spinelli L, Genetti M, Brodbeck V, Momjian S, Schaller K, Vulliemoz S, Seeck M (2013) Electric source imaging of interictal activity accurately localises the seizure onset zone. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2013-305515 PubMedGoogle Scholar
  40. Melani F, Zelmann R, Dubeau F, Gotman J (2013) Occurrence of scalp-fast oscillations among patients with different spiking rate and their role as epileptogenicity marker. Epilepsy Res. doi: 10.1016/j.eplepsyres.2013.06.003 PubMedGoogle Scholar
  41. Michel CM, Murray MM (2012) Towards the utilization of EEG as a brain imaging tool. Neuroimage 61:371–385. doi: 10.1016/j.neuroimage.2011.12.039 PubMedCrossRefGoogle Scholar
  42. Michel CM, Murray MM, Lantz G, Gonzalez S, Spinelli L, Grave De Peralta R (2004a) EEG source imaging. Clin Neurophysiol 10:2195–2222CrossRefGoogle Scholar
  43. Michel CM, Lantz G, Spinelli L, De Peralta RG, Landis T, Seeck M (2004b) 128-Channel EEG source imaging in epilepsy: clinical yield and localization precision. J Clin Neurophysiol 21:71–83PubMedCrossRefGoogle Scholar
  44. Miller KJ, Leuthardt EC, Schalk G, Rao RP, Anderson NR, Moran DW, Miller JW, Ojemann JG (2007) Spectral changes in cortical surface potentials during motor movement. J Neurosci 27(9):2424–2432. doi: 10.1523/JNEUROSCI.3886-06.2007 PubMedCrossRefGoogle Scholar
  45. Oishi M, Otsubo H, Kameyama S, Morota N, Masuda H, Kitayama M, Tanaka R (2002) Epileptic spikes: magnetoencephalography versus simultaneous electrocorticography. Epilepsia 43(11):1390–1395PubMedCrossRefGoogle Scholar
  46. Oostendorp TF, Delbeke J, Stegeman DF (2000) The conductivity of the human skull: results of in vivo and in vitro measurements. IEEE Trans Biomed Eng 47(11):1487–1492. doi: 10.1109/TBME.2000.880100 PubMedCrossRefGoogle Scholar
  47. Ramon C, Holmes MD (2013) Noninvasive epileptic seizure localization from stochastic behavior of short duration interictal high density scalp EEG data. Brain Topogr 1:106–115. doi: 10.1007/s10548-011-0188-8 Google Scholar
  48. Ryynanen OR, Hyttinen JA, Laarne PH, Malmivuo JA (2004) Effect of electrode density and measurement noise on the spatial resolution of cortical potential distribution. IEEE Trans Biomed Eng 51(9):1547–1554. doi: 10.1109/TBME.2004.828036 PubMedCrossRefGoogle Scholar
  49. Staba RJ, Wilson CL, Bragin A, Jhung D, Fried I, Engel J Jr (2004) High-frequency oscillations recorded in human medial temporal lobe during sleep. Ann Neurol 56(1):108–115PubMedCrossRefGoogle Scholar
  50. Storti SF, Boscolo Galazzo I, Del Felice A, Pizzini FB, Arcaro C, Formaggio E, Mai R, Manganotti P (2013) Combining ESI. ASL and PET for quantitative assessment of drug-resistant focal epilepsy. Neuroimage. doi: 10.1016/j.neuroimage.2013.06.028 Google Scholar
  51. Tadel F, Baillet S, Mosher JC, Pantazis D, Leahy RM (2011) Brainstorm: a user-friendly application for MEG/EEG analysis. Comput Intell Neurosci 2011:879716. doi: 10.1155/2011/879716 PubMedCentralPubMedCrossRefGoogle Scholar
  52. Tang C, You F, Cheng G, Gao D, Fu F, Yang G, Dong X (2008) Correlation between structure and resistivity variations of the live human skull. IEEE Trans Biomed Eng 55(9):2286–2292. doi: 10.1109/TBME.2008.923919 PubMedCrossRefGoogle Scholar
  53. Tao JX, Baldwin M, Hawes-Ebersole S, Ebersole JS (2007) Cortical substrates of scalp EEG epileptiform discharges. J Clin Neurophysiol 24(2):96–100PubMedCrossRefGoogle Scholar
  54. Urrestarazu E, Chander R, Dubeau F, Gotman J (2007) Interictal high-frequency oscillations (100–500 Hz) in the intracerebral EEG of epileptic patients. Brain 130(Pt 9):2354–2366PubMedCrossRefGoogle Scholar
  55. von Ellenrieder N, Andrade-Valenca LP, Dubeau F, Gotman J (2012) Automatic detection of fast oscillations (40–200 Hz) in scalp EEG recordings. Clin Neurophysiol 123(4):670–680. doi: 10.1016/j.clinph.2011.07.050 CrossRefGoogle Scholar
  56. Worrell GA, Jerbi K, Kobayashi K, Lina JM, Zelmann R, Le Van Quyen M (2012) Recording and analysis techniques for high-frequency oscillations. Prog Neurobiol. doi: 10.1016/j.pneurobio.2012.02.006 PubMedCentralPubMedGoogle Scholar
  57. Wu JY, Koh S, Sankar R, Mathern GW (2008) Paroxysmal fast activity: an interictal scalp EEG marker of epileptogenesis in children. Epilepsy Res 82(1):99–106. doi: 10.1016/j.eplepsyres.2008.07.010 PubMedCrossRefGoogle Scholar
  58. Yamazaki M, Tucker D, Terrill M, Fujimoto A, Yamamoto T (2013) Dense array EEG (dEEG) source estimation in neocortical epilepsy. Front Neurol 4:42. doi: 10.3389/fneur.2013.00042 PubMedCentralPubMedGoogle Scholar
  59. Yuval-Greenberg S, Tomer O, Keren AS, Nelken I, Deouell LY (2008) Transient induced gamma-band response in EEG as a manifestation of miniature saccades. Neuron 58(3):429–441. doi: 10.1016/j.neuron.2008.03.027 PubMedCrossRefGoogle Scholar
  60. Zelmann R, Mari F, Jacobs J, Zijlmans M, Chander R, Gotman J (2010) Automatic detector of high frequency oscillations for human recordings with macroelectrodes. Conf Proc IEEE Eng Med Biol Soc 2010:2329–2333. doi: 10.1109/IEMBS.2010.5627464 PubMedCentralPubMedGoogle Scholar
  61. Zelmann R, Mari F, Jacobs J, Zijlmans M, Dubeau F, Gotman J (2012) A comparison between detectors of high frequency oscillations. Clin Neurophysiol 123(1):106–116. doi: 10.1016/j.clinph.2011.06.006 PubMedCentralPubMedCrossRefGoogle Scholar
  62. Zijlmans M, Jiruska P, Zelmann R, Leijten FS, Jefferys JG, Gotman J (2012) High-frequency oscillations as a new biomarker in epilepsy. Ann Neurol 71(2):169–178. doi: 10.1002/ana.22548 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • R. Zelmann
    • 1
    Email author
  • J. M. Lina
    • 2
  • A. Schulze-Bonhage
    • 3
  • J. Gotman
    • 1
  • J. Jacobs
    • 3
  1. 1.Montreal Neurological Institute, McGill UniversityMontrealCanada
  2. 2.École de technologie supérieureMontrealCanada
  3. 3.University Hospital FreiburgFreiburgGermany

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