Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity
Studying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123003984 |
| _version_ | 1797364255167610880 |
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| author | Isotta Rigoni Guru Prasad Padmasola Laurent Sheybani Karl Schaller Charles Quairiaux Serge Vulliemoz |
| author_facet | Isotta Rigoni Guru Prasad Padmasola Laurent Sheybani Karl Schaller Charles Quairiaux Serge Vulliemoz |
| author_sort | Isotta Rigoni |
| collection | DOAJ |
| description | Studying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time.Using 32 epicranial electrodes distributed over the mouse hemispheres, we analyzed EEG epochs free from epileptic activity in 15 animals before and 28 days after hippocampal injection (group 1) and in 20 animals on two consecutive days (d28 and d29, group 2). Statistical dependencies between electrodes were characterized with the debiased-weighted phase lag index. We analyzed: a) graph metric changes from baseline to chronic stage (d28) in group 1; b) their reliability across d28 and d29, in group 2; c) their correlation with epileptic activity (EA: seizure, spike and fast-ripple rates), averaged over d28 and d29, in group 2.During the chronic stage, intra-hemispheric connections of the non-injected hemisphere strengthened, yielding an asymmetrical network in low (4–8 Hz) and high theta (8–12 Hz) bands. The contralateral hemisphere also became more integrated and segregated within the high theta band. Both network topology and EEG markers of EA were stable over consecutive days but not correlated with each other.Altogether, we show reproducible large-scale network modifications after the development of focal epilepsy. These modifications are mostly specific to the non-injected hemisphere. The absence of correlation with epileptic activity does not allow to specifically ascribe these network changes to mechanisms supporting EA or rather compensatory inhibition but supports the notion that epilepsy extends beyond the sole repetition of EA and impacts network that might not be involved in EA generation. |
| first_indexed | 2024-03-08T16:32:40Z |
| format | Article |
| id | doaj.art-d0ca0187a833421294708078331e2f3f |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-08T16:32:40Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d0ca0187a833421294708078331e2f3f2024-01-06T04:38:31ZengElsevierNeurobiology of Disease1095-953X2024-01-01190106382Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severityIsotta Rigoni0Guru Prasad Padmasola1Laurent Sheybani2Karl Schaller3Charles Quairiaux4Serge Vulliemoz5EEG and Epilepsy unit, Department of Neuroscience, University Hospital and Faculty of Medicine of Geneva, University of Geneva, Geneva, Switzerland; Corresponding author.Department of Basic Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UKEEG and Epilepsy unit, Department of Neuroscience, University Hospital and Faculty of Medicine of Geneva, University of Geneva, Geneva, Switzerland; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UKDepartment of Neurosurgery, University Hospital and Faculty of Medicine of Geneva, Geneva, SwitzerlandDepartment of Basic Neuroscience, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandEEG and Epilepsy unit, Department of Neuroscience, University Hospital and Faculty of Medicine of Geneva, University of Geneva, Geneva, SwitzerlandStudying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time.Using 32 epicranial electrodes distributed over the mouse hemispheres, we analyzed EEG epochs free from epileptic activity in 15 animals before and 28 days after hippocampal injection (group 1) and in 20 animals on two consecutive days (d28 and d29, group 2). Statistical dependencies between electrodes were characterized with the debiased-weighted phase lag index. We analyzed: a) graph metric changes from baseline to chronic stage (d28) in group 1; b) their reliability across d28 and d29, in group 2; c) their correlation with epileptic activity (EA: seizure, spike and fast-ripple rates), averaged over d28 and d29, in group 2.During the chronic stage, intra-hemispheric connections of the non-injected hemisphere strengthened, yielding an asymmetrical network in low (4–8 Hz) and high theta (8–12 Hz) bands. The contralateral hemisphere also became more integrated and segregated within the high theta band. Both network topology and EEG markers of EA were stable over consecutive days but not correlated with each other.Altogether, we show reproducible large-scale network modifications after the development of focal epilepsy. These modifications are mostly specific to the non-injected hemisphere. The absence of correlation with epileptic activity does not allow to specifically ascribe these network changes to mechanisms supporting EA or rather compensatory inhibition but supports the notion that epilepsy extends beyond the sole repetition of EA and impacts network that might not be involved in EA generation.http://www.sciencedirect.com/science/article/pii/S0969996123003984Hippocampal kainate mouse modelTemporal lobe epilepsyFunctional connectivityEEG |
| spellingShingle | Isotta Rigoni Guru Prasad Padmasola Laurent Sheybani Karl Schaller Charles Quairiaux Serge Vulliemoz Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity Neurobiology of Disease Hippocampal kainate mouse model Temporal lobe epilepsy Functional connectivity EEG |
| title | Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| title_full | Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| title_fullStr | Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| title_full_unstemmed | Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| title_short | Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| title_sort | reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity |
| topic | Hippocampal kainate mouse model Temporal lobe epilepsy Functional connectivity EEG |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123003984 |
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