Paired pulse suppression and facilitation in human epileptogenic hippocampal formation

Wilson, C.L; Khan, S.U; Engel, J; Isokawa, M; Babb, T.L; Behnke, E.J

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Volume 31, Issue 3 , Pages 211-230, August 1998

Paired pulse suppression and facilitation in human epileptogenic hippocampal formation

C.L Wilson
- Department of Neurology, 2155 Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, CA 90024, USA
- The Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA
- Reed Neurological Research Center, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA
- Corresponding author. Tel.: +1 310 8250576; fax: +1 310 2068461; e-mail: clwilson@ucla.edu
S.U Khan
- Department of Neurobiology, Center for the Health Sciences, University of California, Los Angeles, CA 90095 USA
J Engel Jr.
- Department of Neurology, 2155 Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, CA 90024, USA
- Department of Neurobiology, Center for the Health Sciences, University of California, Los Angeles, CA 90095 USA
- The Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA
- Reed Neurological Research Center, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA
M Isokawa
- The Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA
T.L Babb
- Departments of Neuroscience and Neurology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
E.J Behnke
- The Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles CA 90095, USA

Received 10 April 1998; received in revised form 11 May 1998; accepted 11 May 1998.

Abstract

Paired pulse stimulation has commonly been employed to investigate changes in excitability in epileptic hippocampal tissue employing the in vitro slice preparation. We used paired pulse stimulation in the intact temporal lobe of patients with temporal lobe seizures to compare the excitability of pathways in the epileptogenic hippocampus (located in the temporal lobe in which seizures arise) with those in the non-epileptogenic hippocampus of the contralateral temporal lobe (in the hemisphere to which seizures spread). A total of 20 patients with temporal lobe seizure onsets were studied during chronic depth electrode monitoring for seizure localization. Intracranial in vivo stimulation and recording sites included the hippocampus, entorhinal cortex, subicular cortex and parahippocampal gyrus. A comparison of all hippocampal pathways located in the temporal lobe where seizures typically started (n=37) with those in temporal lobes contralateral to seizure onset (n=53) showed significantly greater paired pulse suppression of population post-synaptic potentials on the epileptogenic side (F_(1,87)=6.1, P<0.01). Similarly, mean paired pulse suppression was significantly greater for epileptogenic perforant path responses than for contralateral perforant path responses (F_(1,13)=7.5, P<0.01). In contrast, local stimulation activating intrinsic associational pathways of the epileptogenic hippocampus showed decreased paired pulse suppression in comparison to the epileptogenic perforant path. These results may be a functional consequence of the formation of abnormal recurrent inhibitory and recurrent excitatory pathways in the sclerotic hippocampus. Enhanced inhibition may be adaptive in suppressing seizures during interictal periods, while abnormal recurrent excitatory circuits in the presence of enhanced inhibition may drive the hypersynchronization of principal neurons necessary for seizure genesis.

Keywords: Seizures, Electrical stimulation, Epilepsy, Temporal Lobe, Perforant pathway