GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats

Bouwman, B.M.; Suffczyński, Piotr; Silva, Fernando H. Lopes da; Maris, Eric; Rijn, Clementina M. van

doi:10.1111/j.1460-9568.2007.05533.x

Cited by 22 publications

(14 citation statements)

References 33 publications

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“…Such a re-initiation attempt of the somatosensory cortex might be in accordance with signal analytical results (Maris et al (2006), Bouwman et al (2007)) showing that the chance of getting a new SWD is highest immediately after the previous one. In addition, it seems also to be in line with the above mentioned repetition of SWD frequency modulation that has been found for WAG/Rij rats and in patients during long lasting SWDs (Bosnyakova et al, 2006(Bosnyakova et al, , 2007.…”

Section: Interpretation Of Resultssupporting

confidence: 68%

Termination of ongoing spike-wave discharges investigated by cortico–thalamic network analyses

Lüttjohann

Schoffelen

Luijtelaar

2014

Neurobiology of Disease

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a b s t r a c t a r t i c l e i n f oPurpose: While decades of research were devoted to study generation mechanisms of spontaneous spike and wave discharges (SWD), little attention has been paid to network mechanisms associated with the spontaneous termination of SWD. In the current study coupling-dynamics at the onset and termination of SWD were studied in an extended part of the cortico-thalamo-cortical system of freely moving, genetic absence epileptic WAG/Rij rats. Methods: Local-field potential recordings of 16 male WAG/Rij rats, equipped with multiple electrodes targeting layer 4 to 6 of the somatosensory-cortex (ctx4, ctx5, ctx6), rostral and caudal reticular thalamic nucleus (rRTN & cRTN), ventral postero medial (VPM), anterior-(ATN) and posterior (Po) thalamic nucleus, were obtained. Six seconds lasting pre-SWD-N SWD, SWD-N post SWD and control periods were analyzed with timefrequency methods, and between-region interactions were quantified with frequency-resolved Granger Causality (GC) analysis. Results: Most channel pairs showed increases in GC lasting from onset to offset of the SWD. While for most thalamo-thalamic pairs a dominant coupling direction was found during the complete SWD, most corticothalamic pairs only showed a dominant directional drive (always from cortex to thalamus) during the first 500 ms of SWD. Channel pair ctx4-rRTN showed a longer lasting dominant cortical drive, which stopped 1.5 sec prior to SWD offset. This early decrease in directional coupling was followed by an increase in directional coupling from cRTN to rRTN 1 sec prior to SWD offset. For channel pairs ctx5-Po and ctx6-Po the heightened cortex-N thalamus coupling remained until 1.5 sec following SWD offset, while the thalamus-N cortex coupling for these pairs stopped at SWD offset. Conclusion: The high directional coupling from somatosensory cortex to the thalamus at SWD onset is in good agreement with the idea of a cortical epileptic focus that initiates and entrains other brain structures into seizure activity. The decrease of cortex to rRTN coupling as well as the increased coupling from cRTN to rRTN preceding SWD termination demonstrates that SWD termination is a gradual process that involves both cortico-thalamic as well as intrathalamic processes. The rostral RTN seems to be an important resonator for SWD and relevant for maintenance, while the cRTN might inhibit this oscillation. The somatosensory cortex seems to attempt to reinitiate SWD following its offset via its strong coupling to the posterior thalamus.© 2014 Elsevier Inc. All rights reserved. IntroductionAbsence epilepsy (AE) is a neurological disorder, mostly found in young children, which is characterized by frequent, spontaneously starting and spontaneously stopping, lapses of consciousness. The major electrophysiological characteristic of AE are the spontaneously starting and stopping, rhythmic, generalized, bilateral synchronous spike and wave discharges (SWD), which are known to be generated within the cortico-thalamo-cortical system (Depaulis and v...

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Section: Interpretation Of Resultssupporting

confidence: 68%

Termination of ongoing spike-wave discharges investigated by cortico–thalamic network analyses

Lüttjohann

Schoffelen

Luijtelaar

2014

Neurobiology of Disease

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“…Interestingly, it has been suggested that the balance between GABA A (Cl -) and GABA B (K + )-mediated conductances is essential for the control of SWDs (Kaminski et al, 2001;Marescaux et al, 1992b;Vergnes et al, 1984). The peak frequency of SWDs might be mainly determined by favoring the balance between GABA A and GABA B conductances towards GABA B neurotransmission (Bouwman et al, 2007a;Destexhe and Sejnowski, 2003). Different studies indicate that in TC neurons during absence seizures, (1) GABA A -mediated events are recruited with each SWD, (2) SWD-related activity can be evoked with no significant contribution of GABA B receptors, and (3) blockade of GABA A receptors potentiates SWDrelated activity, presumably through an indirect effect mediated by GABA B receptors (Staak and Pape, 2001).…”

Section: Gabamentioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

128

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Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.09.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial "insult" responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then nongenetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.

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“…Mean-field models have a long history in computational neuroscience (e.g., [26][27][28][29], including many important applications for seizure modeling. These include, for example, mean-field models of absence seizures (30)(31)(32), of depth and surface electrode recordings from patients with temporal lobe epilepsy (33,34), seizure generalization (35), and anesthetic-induced seizures (36).…”

Section: Signatures Of a Critical Transition In A Mean-field Model Ofmentioning

confidence: 99%

Human seizures self-terminate across spatial scales via a critical transition

Kramer

Truccolo

Eden

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

190

147

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Why seizures spontaneously terminate remains an unanswered fundamental question of epileptology. Here we present evidence that seizures self-terminate via a discontinuous critical transition or bifurcation. We show that human brain electrical activity at various spatial scales exhibits common dynamical signatures of an impending critical transition-slowing, increased correlation, and flickering-in the approach to seizure termination. In contrast, prolonged seizures (status epilepticus) repeatedly approach, but do not cross, the critical transition. To support these results, we implement a computational model that demonstrates that alternative stable attractors, representing the ictal and postictal states, emulate the observed dynamics. These results suggest that self-terminating seizures end through a common dynamical mechanism. This description constrains the specific biophysical mechanisms underlying seizure termination, suggests a dynamical understanding of status epilepticus, and demonstrates an accessible system for studying critical transitions in nature.critical slowing down | epilepsy | electrocorticogram | local field potential A lthough extensive observations and research have elucidated some mechanism of seizure initiation and maintenance, how seizures spontaneously terminate remains one of the most important, but still unanswered, questions in epileptology (1). Some of the potential mechanisms of seizure termination (2) include glutamate depletion (3), dynamic changes in ion concentrations (4-6), persistent activation of a hyperpolarization-activated cation conductance (7), changing synaptic effectiveness (5, 8), modulatory effects from subcortical structures and the cerebellum (9), and reduced pH (10). Together, these studies suggest distinct pathways to seizure termination through specific biophysical mechanisms.We propose here a dynamical understanding of seizure termination that encompasses and constrains these and other hypothesized biophysical mechanisms. Specifically, we propose that focal seizures with secondary generalization terminate in a manner consistent with crossing a critical transition or bifurcation in which the system traverses a critical threshold and shifts suddenly to an alternative, attracting dynamical regime (11). Such regime shifts between alternative stable states have been described in many real-world systems (12-14) and exhibit a repertoire of early warning indicators (15-17). The seizing brain provides a unique living system for studying the signatures of an impending critical transition as well as one in which interventions can have profound practical import.We characterize the features of seizure termination in both multiscale in vivo data from patients with epilepsy and a computational model of cortical field activity. We show that population electrical activity-observed at macroscopic spatial scales-exhibits numerous signatures of an impending critical transition, whereas spatially localized recordings of neural spiking activity possess different dynamics. These insi...

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GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats

Cited by 22 publications

References 33 publications

Termination of ongoing spike-wave discharges investigated by cortico–thalamic network analyses

Termination of ongoing spike-wave discharges investigated by cortico–thalamic network analyses

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Human seizures self-terminate across spatial scales via a critical transition

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