Advertisement

Journal of Neurology

, Volume 260, Issue 6, pp 1601–1610 | Cite as

Widespread grey matter changes and hemodynamic correlates to interictal epileptiform discharges in pharmacoresistant mesial temporal epilepsy

  • Roland WiestEmail author
  • Lea Estermann
  • Olivier Scheidegger
  • Christian Rummel
  • Kay Jann
  • Margitta Seeck
  • Kaspar Schindler
  • Martinus Hauf
Original Communication

Abstract

Focal onset epilepsies most often occur in the temporal lobes. To improve diagnosis and therapy of patients suffering from pharmacoresistant temporal lobe epilepsy it is highly important to better understand the underlying functional and structural networks. In mesial temporal lobe epilepsy (MTLE) widespread functional networks are involved in seizure generation and propagation. In this study we have analyzed the spatial distribution of hemodynamic correlates (HC) to interictal epileptiform discharges on simultaneous EEG/fMRI recordings and relative grey matter volume (rGMV) reductions in 10 patients with MTLE. HC occurred beyond the seizure onset zone in the hippocampus, in the ipsilateral insular/operculum, temporo-polar and lateral neocortex, cerebellum, along the central sulcus and bilaterally in the cingulate gyrus. rGMV reductions were detected in the middle temporal gyrus, inferior temporal gyrus and uncus to the hippocampus, the insula, the posterior cingulate and the anterior lobe of the cerebellum. Overlaps between HC and decreased rGMV were detected along the mesolimbic network ipsilateral to the seizure onset zone. We conclude that interictal epileptic activity in MTLE induces widespread metabolic changes in functional networks involved in MTLE seizure activity. These functional networks are spatially overlapping with areas that show a reduction in relative grey matter volumes.

Keywords

Mesial temporal lobe epilepsy EEG/fMRI Network analysis Voxel based morphometry 

Notes

Acknowledgments

We are grateful to M. Fuchs for his support in data collection.

Conflicts of interest

This project was funded by the Swiss National Science Foundation grants [320000-108321/1], [33CM30-140332] and [33CM30-124089]. No additional conflict of interest relevant to this article was reported.

References

  1. 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 57:435–449CrossRefGoogle Scholar
  2. 2.
    Bartolomei F, Chauvel P, Wendling F (2008) Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG. Brain 131:1818–1830PubMedCrossRefGoogle Scholar
  3. 3.
    Bartolomei F, Wendling F, Bellanger JJ, Regis J, Chauvel P (2001) Neural networks involving the medial temporal structures in temporal lobe epilepsy. Clin Neurophysiol 112:1746–1760PubMedCrossRefGoogle Scholar
  4. 4.
    Benuzzi F, Mirandola L, Pugnaghi M, Farinelli V, Tassinari CA, Capovilla G, Cantalupo G, Beccaria F, Nichelli P, Meletti S (2012) Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies. Epilepsia 53:622–630PubMedCrossRefGoogle Scholar
  5. 5.
    Bernhardt BC, Bernasconi N, Concha L, Bernasconi A (2010) Cortical thickness analysis in temporal lobe epilepsy: reproducibility and relation to outcome. Neurology 74:1776–1784PubMedCrossRefGoogle Scholar
  6. 6.
    Blumenfeld H, McNally KA, Vanderhill SD, Paige AL, Chung R, Davis K, Norden AD, Stokking R, Studholme C, Novotny EJ Jr, Zubal IG, Spencer SS (2004) Positive and negative network correlations in temporal lobe epilepsy. Cereb Cortex 14:892–902PubMedCrossRefGoogle Scholar
  7. 7.
    Bonilha L, Edwards JC, Kinsman SL, Morgan PS, Fridriksson J, Rorden C, Rumboldt Z, Roberts DR, Eckert MA, Halford JJ (2010) Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy. Epilepsia 51:519–528PubMedCrossRefGoogle Scholar
  8. 8.
    Bonilha L, Rorden C, Appenzeller S, Coan AC, Cendes F, Li LM (2006) Gray matter atrophy associated with duration of temporal lobe epilepsy. Neuroimage 32:1070–1079PubMedCrossRefGoogle Scholar
  9. 9.
    Carney PW, Masterton RA, Flanagan D, Berkovic SF, Jackson GD (2012) The frontal lobe in absence epilepsy: EEG-fMRI findings. Neurology 78:1157–1165PubMedCrossRefGoogle Scholar
  10. 10.
    Catani M, Jones DK, Donato R, Ffytche DH (2003) Occipito-temporal connections in the human brain. Brain 126:2093–2107PubMedCrossRefGoogle Scholar
  11. 11.
    Chupin M, Hammers A, Liu RS, Colliot O, Burdett J, Bardinet E, Duncan JS, Garnero L, Lemieux L (2009) Automatic segmentation of the hippocampus and the amygdala driven by hybrid constraints: method and validation. Neuroimage 46:749–761PubMedCrossRefGoogle Scholar
  12. 12.
    Coan AC, Appenzeller S, Bonilha L, Li LM, Cendes F (2009) Seizure frequency and lateralization affect progression of atrophy in temporal lobe epilepsy. Neurology 73:834–842PubMedCrossRefGoogle Scholar
  13. 13.
    Cole DM, Smith SM, Beckmann CF (2010) Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci 4:8PubMedGoogle Scholar
  14. 14.
    Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103:13848–13853PubMedCrossRefGoogle Scholar
  15. 15.
    Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134:9–21PubMedCrossRefGoogle Scholar
  16. 16.
    Duzel E, Schiltz K, Solbach T, Peschel T, Baldeweg T, Kaufmann J, Szentkuti A, Heinze HJ (2006) Hippocampal atrophy in temporal lobe epilepsy is correlated with limbic systems atrophy. J Neurol 253:294–300PubMedCrossRefGoogle Scholar
  17. 17.
    Engel J Jr, Brown WJ, Kuhl DE, Phelps ME, Mazziotta JC, Crandall PH (1982) Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol 12:518–528PubMedCrossRefGoogle Scholar
  18. 18.
    Fahoum F, Lopes R, Pittau F, Dubeau F, Gotman J (2012) Widespread epileptic networks in focal epilepsies-EEG-fMRI study. Epilepsia 53(9):1618–1627PubMedCrossRefGoogle Scholar
  19. 19.
    Forman SD, Cohen JD, Fitzgerald M, Eddy WF, Mintun MA, Noll DC (1995) Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med 33:636–647PubMedCrossRefGoogle Scholar
  20. 20.
    Friston KJ, Stephan KE, Lund TE, Morcom A, Kiebel S (2005) Mixed-effects and fMRI studies. Neuroimage 24:244–252PubMedCrossRefGoogle Scholar
  21. 21.
    Gloor P, Olivier A, Quesney LF, Andermann F, Horowitz S (1982) The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Ann Neurol 12:129–144PubMedCrossRefGoogle Scholar
  22. 22.
    Glover GH (1999) Deconvolution of impulse response in event-related BOLD fMRI. Neuroimage 9:416–429PubMedCrossRefGoogle Scholar
  23. 23.
    Gotman J (2008) Epileptic networks studied with EEG-fMRI. Epilepsia 49(Suppl 3):42–51PubMedCrossRefGoogle Scholar
  24. 24.
    Guye M, Regis J, Tamura M, Wendling F, McGonigal A, Chauvel P, Bartolomei F (2006) The role of corticothalamic coupling in human temporal lobe epilepsy. Brain 129:1917–1928PubMedCrossRefGoogle Scholar
  25. 25.
    Hauf M, Jann K, Schindler K, Scheidegger O, Meyer K, Rummel C, Mariani L, Koenig T, Wiest R (2012) Localizing seizure-onset zones in presurgical evaluation of drug-resistant epilepsy by electroencephalography/fMRI: effectiveness of alternative thresholding strategies. AJNR Am J Neuroradiol 33:1818–1824PubMedCrossRefGoogle Scholar
  26. 26.
    Hesse C, James C (2005) Tracking epileptiform activity in the multichannel ictal EEG using spatially constrained independent component analysis. Conf Proc IEEE Eng Med Biol Soc 2:2067–2070PubMedGoogle Scholar
  27. 27.
    Jackson GD, Badawy RA (2011) Selecting patients for epilepsy surgery: identifying a structural lesion. Epilepsy Behav 20:182–189PubMedCrossRefGoogle Scholar
  28. 28.
    Jann K, Kottlow M, Dierks T, Boesch C, Koenig T (2010) Topographic electrophysiological signatures of FMRI resting state networks. PLoS ONE 5:e12945PubMedCrossRefGoogle Scholar
  29. 29.
    Jann K, Wiest R, Hauf M, Meyer K, Boesch C, Mathis J, Schroth G, Dierks T, Koenig T (2008) BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis. Neuroimage 42:635–648PubMedCrossRefGoogle Scholar
  30. 30.
    Keller SS, Mackay CE, Barrick TR, Wieshmann UC, Howard MA, Roberts N (2002) Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy. Neuroimage 16:23–31PubMedCrossRefGoogle Scholar
  31. 31.
    Khan AR, Wang L, Beg MF (2008) FreeSurfer-initiated fully-automated subcortical brain segmentation in MRI using large deformation diffeomorphic metric mapping. Neuroimage 41:735–746PubMedCrossRefGoogle Scholar
  32. 32.
    Kobayashi E, Grova C, Tyvaert L, Dubeau F, Gotman J (2009) Structures involved at the time of temporal lobe spikes revealed by interindividual group analysis of EEG/fMRI data. Epilepsia 50:2549–2556PubMedCrossRefGoogle Scholar
  33. 33.
    Krendl R, Lurger S, Baumgartner C (2008) Absolute spike frequency predicts surgical outcome in TLE with unilateral hippocampal atrophy. Neurology 71:413–418PubMedCrossRefGoogle Scholar
  34. 34.
    Larsen S, Kikinis R, Talos IF, Weinstein D, Wells W, Golby A (2007) Quantitative comparison of functional MRI and direct electrocortical stimulation for functional mapping. Int J Med Robot 3:262–270PubMedCrossRefGoogle Scholar
  35. 35.
    Laufs H, Hamandi K, Salek-Haddadi A, Kleinschmidt AK, Duncan JS, Lemieux L (2007) Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions. Hum Brain Mapp 28:1023–1032PubMedCrossRefGoogle Scholar
  36. 36.
    Li B, Wang X, Yao S, Hu D, Friston K (2012) Task-dependent modulation of effective connectivity within the default mode network. Front Psychol 3:206PubMedCrossRefGoogle Scholar
  37. 37.
    Luders E, Gaser C, Jancke L, Schlaug G (2004) A voxel-based approach to gray matter asymmetries. Neuroimage 22:656–664PubMedCrossRefGoogle Scholar
  38. 38.
    Luo C, Qiu C, Guo Z, Fang J, Li Q, Lei X, Xia Y, Lai Y, Gong Q, Zhou D, Yao D (2011) Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study. PLoS ONE 7:e28196PubMedCrossRefGoogle Scholar
  39. 39.
    Maillard L, Vignal JP, Gavaret M, Guye M, Biraben A, McGonigal A, Chauvel P, Bartolomei F (2004) Semiologic and electrophysiologic correlations in temporal lobe seizure subtypes. Epilepsia 45:1590–1599PubMedCrossRefGoogle Scholar
  40. 40.
    Meisenzahl EM, Koutsouleris N, Gaser C, Bottlender R, Schmitt GJ, McGuire P, Decker P, Burgermeister B, Born C, Reiser M, Moller HJ (2008) Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study. Schizophr Res 102:150–162PubMedCrossRefGoogle Scholar
  41. 41.
    Moorhead TW, Job DE, Spencer MD, Whalley HC, Johnstone EC, Lawrie SM (2005) Empirical comparison of maximal voxel and non-isotropic adjusted cluster extent results in a voxel-based morphometry study of comorbid learning disability with schizophrenia. Neuroimage 28:544–552PubMedCrossRefGoogle Scholar
  42. 42.
    Mueller SG, Laxer KD, Barakos J, Cheong I, Garcia P, Weiner MW (2009) Widespread neocortical abnormalities in temporal lobe epilepsy with and without mesial sclerosis. Neuroimage 46:353–359PubMedCrossRefGoogle Scholar
  43. 43.
    Oakes TR, Fox AS, Johnstone T, Chung MK, Kalin N, Davidson RJ (2007) Integrating VBM into the general linear model with voxelwise anatomical covariates. Neuroimage 34:500–508PubMedCrossRefGoogle Scholar
  44. 44.
    Pail M, Brazdil M, Marecek R, Mikl M (2010) An optimized voxel-based morphometric study of gray matter changes in patients with left-sided and right-sided mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS). Epilepsia 51:511–518PubMedCrossRefGoogle Scholar
  45. 45.
    Riederer F, Lanzenberger R, Kaya M, Prayer D, Serles W, Baumgartner C (2008) Network atrophy in temporal lobe epilepsy: a voxel-based morphometry study. Neurology 71:419–425PubMedCrossRefGoogle Scholar
  46. 46.
    Santana MT, Jackowski AP, da Silva HH, Caboclo LO, Centeno RS, Bressan RA, Carrete H Jr, Yacubian EM (2010) Auras and clinical features in temporal lobe epilepsy: a new approach on the basis of voxel-based morphometry. Epilepsy Res 89:327–338PubMedCrossRefGoogle Scholar
  47. 47.
    Spencer SS (2002) Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia 43:219–227PubMedCrossRefGoogle Scholar
  48. 48.
    Sutula TP, Hagen J, Pitkanen A (2003) Do epileptic seizures damage the brain? Curr Opin Neurol 16:189–195PubMedCrossRefGoogle Scholar
  49. 49.
    Tao JX, Chen XJ, Baldwin M, Yung I, Rose S, Frim D, Hawes-Ebersole S, Ebersole JS (2011) Interictal regional delta slowing is an EEG marker of epileptic network in temporal lobe epilepsy. Epilepsia 52:467–476PubMedCrossRefGoogle Scholar
  50. 50.
    Thiebaut de Schotten M, Urbanski M, Duffau H, Volle E, Levy R, Dubois B, Bartolomeo P (2005) Direct evidence for a parietal-frontal pathway subserving spatial awareness in humans. Science 309:2226–2228PubMedCrossRefGoogle Scholar
  51. 51.
    Vincent JL, Snyder AZ, Fox MD, Shannon BJ, Andrews JR, Raichle ME, Buckner RL (2006) Coherent spontaneous activity identifies a hippocampal-parietal memory network. J Neurophysiol 96:3517–3531PubMedCrossRefGoogle Scholar
  52. 52.
    Voets NL, Beckmann CF, Cole DM, Hong S, Bernasconi A, Bernasconi N (2012) Structural substrates for resting network disruption in temporal lobe epilepsy. Brain 135(Pt 8):2350–2357PubMedCrossRefGoogle Scholar
  53. 53.
    Weder BJ, Schindler K, Loher TJ, 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. Hum Brain Mapp 27:520–534PubMedCrossRefGoogle Scholar
  54. 54.
    Zhang Z, Lu G, Zhong Y, Tan Q, Liao W, Chen Z, Shi J, Liu Y (2009) Impaired perceptual networks in temporal lobe epilepsy revealed by resting fMRI. J Neurol 256:1705–1713PubMedCrossRefGoogle Scholar
  55. 55.
    Zheng J, Qin B, Dang C, Ye W, Chen Z, Yu L (2012) Alertness network in patients with temporal lobe epilepsy: a fMRI study. Epilepsy Res 100:67–73PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Roland Wiest
    • 1
    Email author
  • Lea Estermann
    • 1
  • Olivier Scheidegger
    • 1
  • Christian Rummel
    • 1
  • Kay Jann
    • 2
  • Margitta Seeck
    • 3
  • Kaspar Schindler
    • 4
  • Martinus Hauf
    • 1
    • 5
  1. 1.Support Center of Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, InselpitalUniversity of BernBernSwitzerland
  2. 2.Department of Psychiatric Neurophysiology, University Hospital of PsychiatryUniversity of BernBernSwitzerland
  3. 3.Epilepsy Unit, Department of NeurologyUniversity of GenevaGenevaSwitzerland
  4. 4.Epilepsy Unit, Department of NeurologyUniversity of BernBernSwitzerland
  5. 5.Bethesda Epilepsy ClinicTschuggSwitzerland

Personalised recommendations