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

Clinical article

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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).


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).


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.


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:

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.



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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.


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