Region-specific spreading depolarization drives aberrant post-ictal behavior
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Summary Confusion, aphasia, and unaware wandering are prominent post-ictal symptoms regularly observed in temporal lobe epilepsy (TLE) 1 . Despite the potentially life-threatening nature of the immediate post-ictal state 2 , its neurobiological underpinnings remain understudied 3 . We provide evidence in mice and humans that seizure-associated focal spreading depolarization (sSD) is a pathoclinical key factor in epilepsy. Using two-photon or widefield imaging (hippocampus, neocortex), field potential and single unit recordings, and behavioral assessment in mice, we first studied seizures during viral encephalitis, and subsequently established an optogenetic approach to dissociate hippocampal seizures and SD. We find region-specific occurrence of sSD that displays distinct spatial trajectories to preceding seizures, and show that seizure-related and isolated hippocampal SD prompt post-ictal wandering . This clinically relevant locomotor phenotype occurred in the absence of hippocampal SD progression to the neocortex. Finally, we confirm sSD existence in human epilepsy, in a patient cohort with refractory focal epilepsy, via Behnke-Fried electrode recordings. In this cohort, sSD displayed a similar temporomesial propensity as in mice. This work uncovers sSD as a previously underrecognized pathoclinical entity underlying postictal behavioral abnormalities in epilepsy. Our results carry wide-reaching ramifications for epilepsy research and neurology, and challenge current EEG-standards.
Authors 19
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University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Institute of Biological Information Processing (IBI-3) - Bioelectronics Forschungszentrum, Jülich, Germany; Institute of Biology II, RWTH Aachen University, Aachen, Germany;
Institute of Biological Information Processing (IBI-) - Bioelectronics Forschungszentrum, Jülich, Germany
Institute of Biology II, RWTH Aachen University, Aachen, Germany
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University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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Affiliation as printed
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
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Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
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University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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University of Veterinary Medicine Hannover, Foundation
Affiliation as printed
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany;
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany
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University of Veterinary Medicine Hannover, Foundation
Affiliation as printed
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany;
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany
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University of California, Irvine
Affiliation as printed
Department of Anatomy and Neurobiology, University of California, Irvine, USA;
Department of Anatomy and Neurobiology, University of California, Irvine, USA
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Affiliation as printed
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Institute of Biological Information Processing (IBI-3) - Bioelectronics Forschungszentrum, Jülich, Germany; Institute of Biology II, RWTH Aachen University, Aachen, Germany;
Institute of Biological Information Processing (IBI-) - Bioelectronics Forschungszentrum, Jülich, Germany
Institute of Biology II, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
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Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
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University of Bonn · German Center for Neurodegenerative Diseases
Affiliation as printed
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany
Deutsches Zentrum für Neurodegenerative Erkrankungen e.V., Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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Michael Wenzel corresponding
University of Bonn · University Hospital Bonn
Affiliation as printed
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany; University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany;
University Hospital Bonn, Dept. of Epileptology, Bonn, Germany
University of Bonn, Medical Faculty, Institute of Experimental Epileptology and Cognition Research, Bonn, Germany
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