Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study

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  • 1 Epilepsy Center, University Hospitals Neurological Institute; and
  • | 2 Department of Neurosurgery, Case Medical Center, Cleveland, Ohio
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Object

The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT).

Methods

In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3).

Results

Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdalae on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another.

Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure—namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years.

Conclusions

These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

Abbreviations used in this paper:

AH = anterior hippocampus; APG = anterior parahippocampal gyrus; CG = cingulate gyrus; EEG = electroencephalography; H/P = hippocampal/parahippocampal; HS = hippocampal sclerosis; MH = middle hippocampus; MHT = multiple hippocampal transections; MTLE = mesial temporal lobe epilepsy; PH = posterior hippocampus; PPG = posterior parahippocampal gyrus.

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Contributor Notes

Address correspondence to: Hans O. Lüders, M.D., Ph.D., Epilepsy Center, University Hospitals Neurological Institute, Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106-5040. email: Hans.Luders@UHhospitals.org.

Please include this information when citing this paper: published online December 16, 2011; DOI: 10.3171/2011.10.JNS11261.

  • 1

    Alarcon G, , Garcia Seoane JJ, , Binnie CD, , Martin Miguel MC, , Juler J, & Polkey CE, et al. : Origin and propagation of interictal discharges in the acute electrocorticogram. Implications for pathophysiology and surgical treatment of temporal lobe epilepsy. Brain 120:22592282, 1997

    • Search Google Scholar
    • Export Citation
  • 2

    Amaral DG, & Witter MP: The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571591, 1989

    • Search Google Scholar
    • Export Citation
  • 3

    Anderson P, , Morris R, , Amaral D, , Bliss T, & O'Keefe J: The Hippocampus Book New York, Oxford University Press, 2007

  • 4

    Bartolomei F, , Chauvel P, & Wendling F: Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG. Brain 131:18181830, 2008

    • Search Google Scholar
    • Export Citation
  • 5

    Bartolomei F, , Cosandier-Rimele D, , McGonigal A, , Aubert S, , Régis J, & Gavaret M, et al. : From mesial temporal lobe to temporoperisylvian seizures: a quantified study of temporal lobe seizure networks. Epilepsia 51:21472158, 2010

    • Search Google Scholar
    • Export Citation
  • 6

    Bartolomei F, , Khalil M, , Wendling F, , Sontheimer A, , Régis J, & Ranjeva JP, et al. : Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study. Epilepsia 46:677687, 2005

    • Search Google Scholar
    • Export Citation
  • 7

    Bartolomei F, , Wendling F, , Bellanger JJ, , Régis J, & Chauvel P: Neural networks involving the medial temporal structures in temporal lobe epilepsy. Clin Neurophysiol 112:17461760, 2001

    • Search Google Scholar
    • Export Citation
  • 8

    Bartolomei F, , Wendling F, , Régis J, , Gavaret M, , Guye M, & Chauvel P: Pre-ictal synchronicity in limbic networks of mesial temporal lobe epilepsy. Epilepsy Res 61:89104, 2004

    • Search Google Scholar
    • Export Citation
  • 9

    Bartolomei F, , Wendling F, , Vignal JP, , Kochen S, , Bellanger JJ, & Badier JM, et al. : Seizures of temporal lobe epilepsy: identification of subtypes by coherence analysis using stereo-electroencephalography. Clin Neurophysiol 110:17411754, 1999

    • Search Google Scholar
    • Export Citation
  • 10

    Ben-Ari Y: Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14:375403, 1985

    • Search Google Scholar
    • Export Citation
  • 11

    Bourien J, , Bartolomei F, , Bellanger JJ, , Gavaret M, , Chauvel P, & Wendling F: A method to identify reproducible subsets of coactivated structures during interictal spikes. Application to intracerebral EEG in temporal lobe epilepsy. Clin Neurophysiol 116:443455, 2005

    • Search Google Scholar
    • Export Citation
  • 12

    Cavazos JE, , Jones SM, & Cross DJ: Sprouting and synaptic reorganization in the subiculum and CA1 region of the hippocampus in acute and chronic models of partial-onset epilepsy. Neuroscience 126:677688, 2004

    • Search Google Scholar
    • Export Citation
  • 13

    Demeter S, , Rosene DL, & Van Hoesen GW: Fields of origin and pathways of the interhemispheric commissures in the temporal lobe of macaques. J Comp Neurol 302:2953, 1990

    • Search Google Scholar
    • Export Citation
  • 14

    Duckrow RB, & Spencer SS: Regional coherence and the transfer of ictal activity during seizure onset in the medial temporal lobe. Electroencephalogr Clin Neurophysiol 82:415422, 1992

    • Search Google Scholar
    • Export Citation
  • 15

    Emerson RG, , Turner CA, , Pedley TA, , Walczak TS, & Forgione M: Propagation patterns of temporal spikes. Electroencephalogr Clin Neurophysiol 94:338348, 1995

    • Search Google Scholar
    • Export Citation
  • 16

    Garzon E, & Lüders HO, Cingulate epilepsy. Lüders HO: Textbook of Epilepsy Surgery London, Informa UK, Ltd, 2008. 336340

  • 17

    Gloor P: The Temporal Lobe and the Limbic System New York, Oxford University Press, 1997

  • 18

    Gotman J: Interhemispheric interactions in seizures of focal onset: data from human intracranial recordings. Electroencephalogr Clin Neurophysiol 67:120133, 1987

    • Search Google Scholar
    • Export Citation
  • 19

    Gotman J: Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation. Electroencephalogr Clin Neurophysiol 56:501514, 1983

    • Search Google Scholar
    • Export Citation
  • 20

    Guye M, , Régis J, , Tamura M, , Wendling F, , McGonigal A, & Chauvel P, et al. : The role of corticothalamic coupling in human temporal lobe epilepsy. Brain 129:19171928, 2006

    • Search Google Scholar
    • Export Citation
  • 21

    Hetherington PA, , Austin KB, & Shapiro ML: Ipsilateral associational pathway in the dentate gyrus: an excitatory feedback system that supports N-methyl-D-aspartate-dependent long-term potentiation. Hippocampus 4:422438, 1994

    • Search Google Scholar
    • Export Citation
  • 22

    Holsheimer J, & Lopes da Silva FH: Propagation velocity of epileptiform activity in the hippocampus. Exp Brain Res 77:6978, 1989

  • 23

    Hufnagel A, , Dümpelmann M, , Zentner J, , Schijns O, & Elger CE: Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy. Epilepsia 41:467478, 2000

    • Search Google Scholar
    • Export Citation
  • 24

    Imamura S, , Tanaka S, , Akaike K, , Tojo H, , Takigawa M, & Kuratsu J: Hippocampal transection attenuates kainic acid-induced amygdalar seizures in rats. Brain Res 897:93103, 2001

    • Search Google Scholar
    • Export Citation
  • 25

    Koubeissi MZ, , Jouny CC, , Blakeley JO, & Bergey GK: Analysis of dynamics and propagation of parietal cingulate seizures with secondary mesial temporal involvement. Epilepsy Behav 14:108112, 2009

    • Search Google Scholar
    • Export Citation
  • 26

    Lacruz ME, , García Seoane JJ, , Valentin A, , Selway R, & Alarcón G: Frontal and temporal functional connections of the living human brain. Eur J Neurosci 26:13571370, 2007

    • Search Google Scholar
    • Export Citation
  • 27

    Li XG, , Somogyi P, , Ylinen A, & Buzsáki G: The hippocampal CA3 network: an in vivo intracellular labeling study. J Comp Neurol 339:181208, 1994

    • Search Google Scholar
    • Export Citation
  • 28

    McKhann GM II, , Schoenfeld-McNeill J, , Born DE, , Haglund MM, & Ojemann GA: Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. J Neurosurg 93:4452, 2000

    • Search Google Scholar
    • Export Citation
  • 29

    Miles R, , Traub RD, & Wong RKS: Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus. J Neurophysiol 60:14811496, 1988

    • Search Google Scholar
    • Export Citation
  • 30

    Pallud J, , Devaux B, & Depaulis A: [Changes in spontaneous epileptic activity after selective intrahippocampal transection in a model of chronic mesial temporal lobe epilepsy.]. Neurochirurgie 54:135140, 2008. (Fr)

    • Search Google Scholar
    • Export Citation
  • 31

    Pandya DN, & Seltzer B, The topography of commissural fibers. Lepre F, , Ptito M, & Jasper HH: Two Hemispheres, One Brain: Functions of the Corpus Callosum: Proceedings of the Sixth International Symposium of the Centre de recherche en sciences neurologique New York, Alan R. Liss, 1986. 4773

    • Search Google Scholar
    • Export Citation
  • 32

    Scoville WB, & Milner B: Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:1121, 1957

  • 33

    Shimizu H, , Kawai K, , Sunaga S, , Sugano H, & Yamada T: Hippocampal transection for treatment of left temporal lobe epilepsy with preservation of verbal memory. J Clin Neurosci 13:322328, 2006

    • Search Google Scholar
    • Export Citation
  • 34

    Siegel AM, , Wieser HG, , Wichmann W, & Yaşargil GM: Relationships between MR-imaged total amount of tissue removed, resection scores of specific mediobasal limbic subcompartments and clinical outcome following selective amygdalohippocampectomy. Epilepsy Res 6:5665, 1990

    • Search Google Scholar
    • Export Citation
  • 35

    Soleng AF, , Raastad M, & Andersen P: Conduction latency along CA3 hippocampal axons from rat. Hippocampus 13:953961, 2003

  • 36

    Spencer SS, & Spencer DD: Entorhinal-hippocampal interactions in medial temporal lobe epilepsy. Epilepsia 35:721727, 1994

  • 37

    Wilson CL, , Isokawa M, , Babb TL, , Crandall PH, , Levesque MF, & Engel J Jr: Functional connections in the human temporal lobe. II Evidence for a loss of functional linkage between contralateral limbic structures. Exp Brain Res 85:174187, 1991

    • Search Google Scholar
    • Export Citation
  • 38

    Witter MP, & Amaral DG: Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex. J Comp Neurol 307:437459, 1991

    • Search Google Scholar
    • Export Citation
  • 39

    Zeki SM: Comparison of the cortical degeneration in the visual regions of the temporal lobe of the monkey following section of the anterior commissure and the splenium. J Comp Neurol 148:167175, 1973

    • Search Google Scholar
    • Export Citation

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