Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy
IntroductionGenetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-fun...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1355862/full |
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| author | Lydia Wachsmuth Leo Hebbelmann Jutta Prade Laura C. Kohnert Henriette Lambers Annika Lüttjohann Thomas Budde Andreas Hess Andreas Hess Andreas Hess Cornelius Faber |
| author_facet | Lydia Wachsmuth Leo Hebbelmann Jutta Prade Laura C. Kohnert Henriette Lambers Annika Lüttjohann Thomas Budde Andreas Hess Andreas Hess Andreas Hess Cornelius Faber |
| author_sort | Lydia Wachsmuth |
| collection | DOAJ |
| description | IntroductionGenetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-functional magnetic resonance imaging (rs-fMRI) and manganese-enhanced MRI (MEMRI) combined with morphometry, and to investigate potential brain network alterations, following long-term seizure activity.MethodsRepeated rs-fMRI measurements at 9.4 T between 3 and 8 months of age were combined with MEMRI at the final time point of the study. We used graph theory analysis to infer community structure and global and local network parameters from rs-fMRI data and compared them to brain region-wise manganese accumulation patterns and deformation-based morphometry (DBM).ResultsFunctional connectivity (FC) was generally higher in GAERS when compared to NEC. Global network parameters and community structure were similar in NEC and GAERS, suggesting efficiently functioning networks in both strains. No progressive FC changes were observed in epileptic animals. Network-based statistics (NBS) revealed stronger FC within the cortical community, including regions of association and sensorimotor cortex, and with basal ganglia and limbic regions in GAERS, irrespective of age. Higher manganese accumulation in GAERS than in NEC was observed at 8 months of age, consistent with higher overall rs-FC, particularly in sensorimotor cortex and association cortex regions. Functional measures showed less similarity in subcortical regions. Whole brain volumes of 8 months-old GAERS were higher when compared to age-matched NEC, and DBM revealed increased volumes of several association and sensorimotor cortex regions and of the thalamus.Discussionrs-fMRI, MEMRI, and volumetric data collectively suggest the significance of cortical networks in GAERS, which correlates with an increased fronto-central connectivity in childhood absence epilepsy (CAE). Our findings also verify involvement of basal ganglia and limbic regions. Epilepsy-related network alterations are already present in juvenile animals. Consequently, this early condition seems to play a greater role in dynamic brain function than chronic absence seizures. |
| first_indexed | 2024-04-25T01:00:53Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-25T01:00:53Z |
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| spelling | doaj.art-c5decd9743e14e2bace3bb18abbc98742024-03-11T05:04:39ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-03-011510.3389/fneur.2024.13558621355862Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsyLydia Wachsmuth0Leo Hebbelmann1Jutta Prade2Laura C. Kohnert3Henriette Lambers4Annika Lüttjohann5Thomas Budde6Andreas Hess7Andreas Hess8Andreas Hess9Cornelius Faber10Clinic of Radiology, University of Münster, Münster, GermanyClinic of Radiology, University of Münster, Münster, GermanyDepartment of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyClinic of Radiology, University of Münster, Münster, GermanyInstitute of Physiology I, University of Münster, Münster, GermanyInstitute of Physiology I, University of Münster, Münster, GermanyDepartment of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyDepartment of Neuroradiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyFAU NeW – Research Center for New Bioactive Compounds, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyClinic of Radiology, University of Münster, Münster, GermanyIntroductionGenetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-functional magnetic resonance imaging (rs-fMRI) and manganese-enhanced MRI (MEMRI) combined with morphometry, and to investigate potential brain network alterations, following long-term seizure activity.MethodsRepeated rs-fMRI measurements at 9.4 T between 3 and 8 months of age were combined with MEMRI at the final time point of the study. We used graph theory analysis to infer community structure and global and local network parameters from rs-fMRI data and compared them to brain region-wise manganese accumulation patterns and deformation-based morphometry (DBM).ResultsFunctional connectivity (FC) was generally higher in GAERS when compared to NEC. Global network parameters and community structure were similar in NEC and GAERS, suggesting efficiently functioning networks in both strains. No progressive FC changes were observed in epileptic animals. Network-based statistics (NBS) revealed stronger FC within the cortical community, including regions of association and sensorimotor cortex, and with basal ganglia and limbic regions in GAERS, irrespective of age. Higher manganese accumulation in GAERS than in NEC was observed at 8 months of age, consistent with higher overall rs-FC, particularly in sensorimotor cortex and association cortex regions. Functional measures showed less similarity in subcortical regions. Whole brain volumes of 8 months-old GAERS were higher when compared to age-matched NEC, and DBM revealed increased volumes of several association and sensorimotor cortex regions and of the thalamus.Discussionrs-fMRI, MEMRI, and volumetric data collectively suggest the significance of cortical networks in GAERS, which correlates with an increased fronto-central connectivity in childhood absence epilepsy (CAE). Our findings also verify involvement of basal ganglia and limbic regions. Epilepsy-related network alterations are already present in juvenile animals. Consequently, this early condition seems to play a greater role in dynamic brain function than chronic absence seizures.https://www.frontiersin.org/articles/10.3389/fneur.2024.1355862/fullGAERSabsence epilepsygraph theoryfunctional connectivityrs-fMRIMEMRI |
| spellingShingle | Lydia Wachsmuth Leo Hebbelmann Jutta Prade Laura C. Kohnert Henriette Lambers Annika Lüttjohann Thomas Budde Andreas Hess Andreas Hess Andreas Hess Cornelius Faber Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy Frontiers in Neurology GAERS absence epilepsy graph theory functional connectivity rs-fMRI MEMRI |
| title | Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy |
| title_full | Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy |
| title_fullStr | Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy |
| title_full_unstemmed | Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy |
| title_short | Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy |
| title_sort | epilepsy related functional brain network alterations are already present at an early age in the gaers rat model of genetic absence epilepsy |
| topic | GAERS absence epilepsy graph theory functional connectivity rs-fMRI MEMRI |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1355862/full |
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