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Three-dimensional surface maps link local atrophy and fast ripples in human epileptic hippocampus

Authors

  • Jennifer A. Ogren PhD,

    1. Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Charles L. Wilson PhD,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    2. Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Anatol Bragin PhD,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    2. Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Jack J. Lin MD,

    1. Department of Neurology, UCI School of Medicine, Irvine, CA
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  • Noriko Salamon MD,

    1. Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Rebecca A. Dutton BS,

    1. Laboratory of Neuro Imaging (LONI), David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Eileen Luders PhD,

    1. Laboratory of Neuro Imaging (LONI), David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Tony A. Fields BS,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Itzhak Fried MD, PhD,

    1. Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Arthur W. Toga PhD,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    2. Laboratory of Neuro Imaging (LONI), David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Paul M. Thompson PhD,

    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    2. Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
    3. Laboratory of Neuro Imaging (LONI), David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Jerome Engel Jr MD, PhD,

    1. Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    3. Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA
    4. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA
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  • Richard J. Staba PhD

    Corresponding author
    1. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    • Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Room 2155, Los Angeles, CA 90095-7169
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  • Potential conflict of interest: Nothing to report.

Abstract

Objectives

There is compelling evidence that pathological high-frequency oscillations (HFOs), called fast ripples (FR, 150–500Hz), reflect abnormal synchronous neuronal discharges in areas responsible for seizure genesis in patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that morphological changes associated with hippocampal atrophy (HA) contribute to the generation of FR, yet there is limited evidence that hippocampal FR-generating sites correspond with local areas of atrophy.

Methods

Interictal HFOs were recorded from hippocampal microelectrodes in 10 patients with MTLE. Rates of FR and ripple discharge from each microelectrode were evaluated in relation to local measures of HA obtained using 3-dimensional magnetic resonance imaging (MRI) hippocampal modeling.

Results

Rates of FR discharge were 3 times higher in areas of significant local HA compared with rates in nonatrophic areas. Furthermore, FR occurrence correlated directly with the severity of damage in these local atrophic regions. In contrast, we found no difference in rates of ripple discharge between local atrophic and nonatrophic areas.

Interpretation

The proximity between local HA and microelectrode-recorded FR suggests that morphological changes such as neuron loss and synaptic reorganization may contribute to the generation of FR. Pathological HFOs, such as FR, may provide a reliable surrogate marker of abnormal neuronal excitability in hippocampal areas responsible for the generation of spontaneous seizures in patients with MTLE. Based on these data, it is possible that MRI-based measures of local HA could identify FR-generating regions, and thus provide a noninvasive means to localize epileptogenic regions in hippocampus. Ann Neurol 2009;66:783–791

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