Hippocampal and Entorhinal Cortex High-Frequency Oscillations (100–500 Hz) in Human Epileptic Brain and in Kainic Acid-Treated Rats with Chronic Seizures

Authors

  • Anatol Bragin,

    Corresponding author
    1. Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California, U.S.A.
    2. Department of Neurology, UCLA School of Medicine, Los Angeles, California, U.S.A.
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  • Jerome Engel Jr.,

    1. Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California, U.S.A.
    2. Department of Neurology, UCLA School of Medicine, Los Angeles, California, U.S.A.
    3. Brain Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A.
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  • Charles L. Wilson,

    1. Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California, U.S.A.
    2. Department of Neurology, UCLA School of Medicine, Los Angeles, California, U.S.A.
    3. Brain Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A.
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  • Itzhak Fried,

    1. Division of Neurosurgery, UCLA School of Medicine, Los Angeles, California, U.S.A.
    2. Brain Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A.
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  • Gary W. Mathern

    1. Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California, U.S.A.
    2. Division of Neurosurgery, UCLA School of Medicine, Los Angeles, California, U.S.A.
    3. Brain Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A.
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  • Permanent address of Dr. Bragin: Institute of Experimental and Theoretical Biophysics, Puschino, Russia.

Address correspondence and reprint requests to Dr. I. Engel, Jr. at Reed Neurological Research Center, Department of Neurology, 710 Westwood Plaza, UCLA School of Medicine, Los Angeles, CA 90095-1769, U.S.A.

Abstract

Summary: Purpose: Properties of oscillations with frequencies >100 Hz were studied in kainic acid (KA)-treated rats and compared with those recorded in normal and kindled rats as well as in patients with epilepsy to determine differences associated with epilepsy.

Methods: Prolonged in vivo wideband recordings of electrical activity were made in hippocampus and entorhinal cortex (EC) of (a) normal rats, (b) kindled rats, (c) rats having chronic recurrent spontaneous seizures after intrahippocampal KA injections, and (d) patients with epilepsy undergoing depth electrode evaluation in preparation for surgical treatment.

Results: Intermittent oscillatory activity ranging from 100 to 200 Hz in frequency and 50–150 ms in duration was recorded in CA1 and EC of all three animal groups, and in epileptic human hippocampus and EC. This activity had the same characteristics in all groups, resembled previously observed “ripples” described by Buzsáki et al., and appeared to represent field potentials of inhibitory postsynaptic potentials (IPSPs) on principal cells. Unexpectedly, higher frequency intermittent oscillatory activity ranging from 200 to 500 Hz and 10–100 ms in duration was encountered only in KA-treated rats and patients with epilepsy. These oscillations, termed fast ripples (FRs), were found only adjacent to the epileptogenic lesion in hippocampus, EC, and dentate gyrus, and appeared to represent field potential population spikes. Their local origin was indicated by correspondence with the negative phase of burst discharges of putative pyramidal cells.

Conclusions: The persistence of normal-appearing ripples in epileptic brain support the view that inhibitory processes are preserved. FRs appear to be field potentials reflecting hypersynchronous bursting of excitatory neurons and provide an opportunity to study the role of this pathophysiologic phenomenon in epilepsy and seizure initiation. Furthermore, if FR activity is unique to brain areas capable of generating spontaneous seizures, its identification could be a powerful functional indicator of the epileptic region in patients evaluated for surgical treatment.

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