Subtle alterations in memory systems and normal visual attention in the GAERS model of absence epilepsy

Marques-Carneiro, José Eduardo; Faure, J; Barbelivien, Alexandra; Nehlig, Astrid; Cassel, Jean‐Christophe

doi:10.1016/j.neuroscience.2015.12.048

Cited by 11 publications

(6 citation statements)

References 30 publications

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“…Interestingly, we observed a consistent mesial-temporal lobe volume reduction both with VBM and Freesurfer analyses. This finding is in accordance with recent studies showing hippocampal damage and spatial memory deficits in animal models of absence epilepsy ( Arcaro et al, 2016 , Jafarian et al, 2015 , Marques-Carneiro et al, 2016 ). However, human data on memory impairment in absence epilepsy are still conflicting ( Verrotti et al, 2015 ) and specific studies focusing on cognitive-brain structure correlation should be performed to better analyse this issue.…”

Section: Discussionsupporting

confidence: 93%

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

Tondelli

Vaudano

Ruggieri

et al. 2016

NeuroImage: Clinical

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Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE) in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM) and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory.

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Section: Discussionsupporting

confidence: 93%

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

Tondelli

Vaudano

Ruggieri

et al. 2016

NeuroImage: Clinical

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“…Absence seizure models do show psychiatric comorbidities, providing additional validity to these models and a means for future mechanistic studies into these conditions. Subtle alterations in attention, that may be task-specific, have been reported in GAERS ( Marques-Carneiro et al , 2016 ; Marks et al , 2016 a , b ) and WAG/Rij rats ( Karson et al , 2012 ; Jafarian et al , 2015 ), but the majority of the animal studies has focused on anxiety‐ and depression-like behaviours that have been consistently observed in GAERS ( Jones et al , 2008 ; Bouilleret et al , 2009 , Powell et al , 2009 , 2014 a , b ; Tringham et al , 2012 ; Dezsi et al , 2013 ; Marques-Carneiro et al , 2014 ) and WAG/Rij rats ( Sarkisova et al , 2010 ; Russo et al , 2011 ; van Luijtelaar et al , 2013 ; Moyanova et al , 2018 ). Notably, anxiety and absence seizures in GAERS rats can be reduced by environmental enrichment and these anxiolytic and anti-epileptogenic effects are heritable into the next generation ( Dezsi et al , 2016 ), prompting future investigations on potential epigenetic contributions to human absence seizures and their comorbidity.…”

Section: Introductionmentioning

confidence: 91%

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures

Crunelli

Lőrincz

McCafferty

et al. 2020

Brain

150

159

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Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities.

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“…2009 ). Learning and memory deficits have been observed more recently in GAERS ( Marques-Carneiro et al. 2016 ) and in WAG/Rij rats ( Karson et al.…”

Section: Introductionmentioning

confidence: 98%

Retrosplenial Cortex Contributes to Network Changes during Seizures in the GAERS Absence Epilepsy Rat Model

Wachsmuth

Datunashvili

Kemper

et al. 2021

Cerebral Cortex Communications

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Resting state-fMRI (rs-fMRI) was performed to explore brain networks in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and in non-epileptic controls (NEC) during monitoring of the brain state by simultaneous optical Ca2+-recordings. Graph theoretical analysis allowed for identification of acute and chronic network changes and revealed preserved small world topology before and after seizure onset. The most prominent acute change in network organization during seizures was the segregation of cortical regions from the remaining brain. Stronger connections between thalamic with limbic regions compared to pre-seizure state indicated network regularization during seizures. When comparing between strains, intra-thalamic connections were prominent in NEC, on local level represented by higher thalamic strengths and hub scores. Subtle differences were observed for retrosplenial cortex (RS), forming more connections beyond cortex in epileptic rats, and showing a tendency to lateralization during seizures. A potential role of RS as hub between subcortical and cortical regions in epilepsy was supported by increased numbers of parvalbumin-positive (PV+) interneurons together with enhanced inhibitory synaptic activity and neuronal excitability in pyramidal neurons. By combining multimodal fMRI data, graph theoretical methods, and electrophysiological recordings we identified the RS as promising target for modulation of seizure activity and/or comorbidities.

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Subtle alterations in memory systems and normal visual attention in the GAERS model of absence epilepsy

Cited by 11 publications

References 30 publications

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures

Retrosplenial Cortex Contributes to Network Changes during Seizures in the GAERS Absence Epilepsy Rat Model

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