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

Clinical article

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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.

Article Information

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.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Case 5. Axial T1-weighted MR images coregistered with postoperative CT scans by using BrainLAB iPlan, version 2.6 (Brain-Lab Software). The location of each contact of hippocampal depth electrodes is seen. Not all of the contacts are apparent in this figure because the plane of the cut was different from the plane of the depth electrode probes. The numbers 1–4 and 1–7 are the numbers assigned to electrodes. LAH = left AH; LMH = left MH; LPH = left PH.

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    A: Intraoperative photograph obtained in the patient in Case 5. The left hippocampal body with sphenoidal electrodes is seen. Electrodes 2, 3, and 4 (E2, E3, and E4) are shown. Single arrow: the first transection, between electrodes 1 and 2. Double arrows: the second transection, between electrodes 2 and 3. B–D: Graphs showing the spike before and after transections during MHT in Cases 1, 5, and 6. A striking decrease of the spike frequency (no./min) can be seen after the first or second transection in all cases. The designation “MHT X/Y” means hippocampal transection between electrode X and Y; “MHT /X” and “MHT X/” mean hippocampal transection at the region 2.5 mm anterior and posterior, respectively, to electrode X.

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    Case 5. Results of statistical analysis of ictal epileptiform discharges between the following structures: AH and MH (A), AH and PH (B), MH and PH (C), and AH and APG (D). The upper graph in each panel shows cross-correlation and the lower graph shows the time-shift index. A striking and persistent increase of cross-correlation occurred after the EEG seizure onset in every analysis. On the other hand, the time shift during seizures showed slowly changing values, with relatively short duration of positive and negative time shifts. Sz = seizure.

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    Bar graphs showing results of pre- and postoperative neuropsychological examinations in Cases 1, 5, and 6. The black bar and the white bar indicate scores before and 15 months after MHT, respectively. The patient in Case 5, who had the most proficient naming and verbal memory scores presurgically, showed some decline in naming and verbal memory, as well as mild reduction in verbal IQ score. For the other patients, naming, reading, verbal and spatial memory, and verbal and spatial IQ were largely stable. BNT = Boston Naming Test; WAIS = Wechsler Adult Intelligence Scale; WMS = Wisconsin Memory Scale.

References

  • 1

    Alarcon GGarcia Seoane JJBinnie CDMartin Miguel MCJuler JPolkey CE: Origin and propagation of interictal discharges in the acute electrocorticogram. Implications for pathophysiology and surgical treatment of temporal lobe epilepsy. Brain 120:225922821997

  • 2

    Amaral DGWitter MP: The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:5715911989

  • 3

    Anderson PMorris RAmaral DBliss TO'Keefe J: The Hippocampus Book New YorkOxford University Press2007

  • 4

    Bartolomei FChauvel PWendling F: Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG. Brain 131:181818302008

  • 5

    Bartolomei FCosandier-Rimele DMcGonigal AAubert SRégis JGavaret M: From mesial temporal lobe to temporoperisylvian seizures: a quantified study of temporal lobe seizure networks. Epilepsia 51:214721582010

  • 6

    Bartolomei FKhalil MWendling FSontheimer ARégis JRanjeva JP: Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study. Epilepsia 46:6776872005

  • 7

    Bartolomei FWendling FBellanger JJRégis JChauvel P: Neural networks involving the medial temporal structures in temporal lobe epilepsy. Clin Neurophysiol 112:174617602001

  • 8

    Bartolomei FWendling FRégis JGavaret MGuye MChauvel P: Pre-ictal synchronicity in limbic networks of mesial temporal lobe epilepsy. Epilepsy Res 61:891042004

  • 9

    Bartolomei FWendling FVignal JPKochen SBellanger JJBadier JM: Seizures of temporal lobe epilepsy: identification of subtypes by coherence analysis using stereo-electroencephalography. Clin Neurophysiol 110:174117541999

  • 10

    Ben-Ari Y: Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14:3754031985

  • 11

    Bourien JBartolomei FBellanger JJGavaret MChauvel PWendling F: A method to identify reproducible subsets of coactivated structures during interictal spikes. Application to intracerebral EEG in temporal lobe epilepsy. Clin Neurophysiol 116:4434552005

  • 12

    Cavazos JEJones SMCross DJ: Sprouting and synaptic reorganization in the subiculum and CA1 region of the hippocampus in acute and chronic models of partial-onset epilepsy. Neuroscience 126:6776882004

  • 13

    Demeter SRosene DLVan Hoesen GW: Fields of origin and pathways of the interhemispheric commissures in the temporal lobe of macaques. J Comp Neurol 302:29531990

  • 14

    Duckrow RBSpencer SS: Regional coherence and the transfer of ictal activity during seizure onset in the medial temporal lobe. Electroencephalogr Clin Neurophysiol 82:4154221992

  • 15

    Emerson RGTurner CAPedley TAWalczak TSForgione M: Propagation patterns of temporal spikes. Electroencephalogr Clin Neurophysiol 94:3383481995

  • 16

    Garzon ELüders HOCingulate epilepsy. Lüders HO: Textbook of Epilepsy Surgery LondonInforma UK, Ltd2008. 336340

  • 17

    Gloor P: The Temporal Lobe and the Limbic System New YorkOxford University Press1997

  • 18

    Gotman J: Interhemispheric interactions in seizures of focal onset: data from human intracranial recordings. Electroencephalogr Clin Neurophysiol 67:1201331987

  • 19

    Gotman J: Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation. Electroencephalogr Clin Neurophysiol 56:5015141983

  • 20

    Guye MRégis JTamura MWendling FMcGonigal AChauvel P: The role of corticothalamic coupling in human temporal lobe epilepsy. Brain 129:191719282006

  • 21

    Hetherington PAAustin KBShapiro ML: Ipsilateral associational pathway in the dentate gyrus: an excitatory feedback system that supports N-methyl-D-aspartate-dependent long-term potentiation. Hippocampus 4:4224381994

  • 22

    Holsheimer JLopes da Silva FH: Propagation velocity of epileptiform activity in the hippocampus. Exp Brain Res 77:69781989

  • 23

    Hufnagel ADümpelmann MZentner JSchijns OElger CE: Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy. Epilepsia 41:4674782000

  • 24

    Imamura STanaka SAkaike KTojo HTakigawa MKuratsu J: Hippocampal transection attenuates kainic acid-induced amygdalar seizures in rats. Brain Res 897:931032001

  • 25

    Koubeissi MZJouny CCBlakeley JOBergey GK: Analysis of dynamics and propagation of parietal cingulate seizures with secondary mesial temporal involvement. Epilepsy Behav 14:1081122009

  • 26

    Lacruz MEGarcía Seoane JJValentin ASelway RAlarcón G: Frontal and temporal functional connections of the living human brain. Eur J Neurosci 26:135713702007

  • 27

    Li XGSomogyi PYlinen ABuzsáki G: The hippocampal CA3 network: an in vivo intracellular labeling study. J Comp Neurol 339:1812081994

  • 28

    McKhann GM IISchoenfeld-McNeill JBorn DEHaglund MMOjemann GA: Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. J Neurosurg 93:44522000

  • 29

    Miles RTraub RDWong RKS: Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus. J Neurophysiol 60:148114961988

  • 30

    Pallud JDevaux BDepaulis A: [Changes in spontaneous epileptic activity after selective intrahippocampal transection in a model of chronic mesial temporal lobe epilepsy.]. Neurochirurgie 54:1351402008. (Fr)

  • 31

    Pandya DNSeltzer BThe topography of commissural fibers. Lepre FPtito MJasper 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 YorkAlan R. Liss1986. 4773

  • 32

    Scoville WBMilner B: Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:11211957

  • 33

    Shimizu HKawai KSunaga SSugano HYamada T: Hippocampal transection for treatment of left temporal lobe epilepsy with preservation of verbal memory. J Clin Neurosci 13:3223282006

  • 34

    Siegel AMWieser HGWichmann WYaşargil 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 6:56651990

  • 35

    Soleng AFRaastad MAndersen P: Conduction latency along CA3 hippocampal axons from rat. Hippocampus 13:9539612003

  • 36

    Spencer SSSpencer DD: Entorhinal-hippocampal interactions in medial temporal lobe epilepsy. Epilepsia 35:7217271994

  • 37

    Wilson CLIsokawa MBabb TLCrandall PHLevesque MFEngel J Jr: Functional connections in the human temporal lobe. II Evidence for a loss of functional linkage between contralateral limbic structures. Exp Brain Res 85:1741871991

  • 38

    Witter MPAmaral DG: Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex. J Comp Neurol 307:4374591991

  • 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 148:1671751973

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