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

The 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 non-genetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling

Protostellar collapse: rotation and disk formation

We present some important conclusions from recent calculations pertaining to the collapse of rotating molecular cloud cores with axial symmetry, corresponding to evolution of young stellar objects through classes 0 and begin of class I. Three main issues have been addressed: (1) The typical timescale for building up a preplanetary disk - once more it turned out that it is of the order of one free-fall time which is decisively shorter than the widely assumed timescale related to the so-called 'inside-out collapse'; (2) Redistribution of angular momentum and the accompanying dissipation of kinetic (rotational) energy - together these processes govern the mechanical and thermal evolution of the protostellar core to a large extent; (3) The origin of calcium-aluminium-rich inclusions (CAIs) - due to the specific pattern of the accretion flow, material that has undergone substantial chemical and mineralogical modifications in the hot (exceeding 900 K) interior of the protostellar core may have a good chance to be advectively transported outward into the cooler remote parts (beyond 4 AU, say) of the growing disk and to survive there until it is incorporated into a meteoritic body.Comment: 4 pages, 4 figure

Statistical Properties and Predictability of Extreme Epileptic Events

The use of extreme events theory for the analysis of spontaneous epileptic brain activity is a relevant multidisciplinary problem. It allows deeper understanding of pathological brain functioning and unraveling mechanisms underlying the epileptic seizure emergence along with its predictability. The latter is a desired goal in epileptology which might open the way for new therapies to control and prevent epileptic attacks. With this goal in mind, we applied the extreme event theory for studying statistical properties of electroencephalographic (EEG) recordings of WAG/Rij rats with genetic predisposition to absence epilepsy. Our approach allowed us to reveal extreme events inherent in this pathological spiking activity, highly pronounced in a particular frequency range. The return interval analysis showed that the epileptic seizures exhibit a highly-structural behavior during the active phase of the spiking activity. Obtained results evidenced a possibility for early (up to 7 s) prediction of epileptic seizures based on consideration of EEG statistical properties

Increasing Human Performance by Sharing Cognitive Load Using Brain-to-Brain Interface

Brain-computer interfaces (BCIs) attract a lot of attention because of their ability to improve the brain's efficiency in performing complex tasks using a computer. Furthermore, BCIs can increase human's performance not only due to human-machine interactions, but also thanks to an optimal distribution of cognitive load among all members of a group working on a common task, i.e., due to human-human interaction. The latter is of particular importance when sustained attention and alertness are required. In every day practice, this is a common occurrence, for example, among office workers, pilots of a military or a civil aircraft, power plant operators, etc. Their routinely work includes continuous monitoring of instrument readings and implies a heavy cognitive load due to processing large amounts of visual information. In this paper, we propose a brain-to-brain interface (BBI) which estimates brain states of every participant and distributes a cognitive load among all members of the group accomplishing together a common task. The BBI allows sharing the whole workload between all participants depending on their current cognitive performance estimated from their electrical brain activity. We show that the team efficiency can be increased due to redistribution of the work between participants so that the most difficult workload falls on the operator who exhibits maximum performance. Finally, we demonstrate that the human-to-human interaction is more efficient in the presence of a certain delay determined by brain rhythms. The obtained results are promising for the development of a new generation of communication systems based on neurophysiological brain activity of interacting people. Such BBIs will distribute a common task between all group members according to their individual physical conditions

Danielle Jacquart et Françoise Micheau. La médecine arabe et l'Occident médiéval. Paris : Maisonneuve et Larose, 1990. In-8°, 271 pages. (Collection Islam-Occident, 7.)

Danielle Jacquart et Françoise Micheau. La médecine arabe et l'Occident médiéval. Paris : Maisonneuve et Larose, 1990. In-8°, 271 pages. (Collection Islam-Occident, 7.). In: Bibliothèque de l'école des chartes. 1996, tome 154, livraison 1. pp. 278-281

Is there a future for mGlu5-positive allosteric modulators in absence epilepsy? A comparison with ethosuximide

Contains fulltext : 175798.pdf (Publisher’s version ) (Open Access)Ethosuximide is the drug of choice in the treatment of various types of absence seizures. However, there is plenty of room for other anti-absence drugs, considering that not all subjects (57-74%) become seizure-free and about 47% of ethosuximide therapy fails. New anti-absence drugs may target or modulate glutamatergic and or GABAergic neurotransmission, the key players in the circuitry involved in the cortico-thalamo-cortical oscillations responsible for the highly stereotyped spike-wave discharges (SWDs). Cortical highly excitable cells in the focal region form the trigger for the occurrence of SWDs. In contrast, enhanced tonic inhibition is dominant in the thalamus. Biochemical studies have shown that symptomatic WAG/Rij rats differ from age-matched controls in metabotropic glutamate (mGlu) receptor expression and function: mGlu5 receptor expression and function are increased in the somatosensory cortex, and mGlu1 receptor expression is decreased in the thalamus. The two group I mGlu receptor-positive allosteric modulators (PAMs) VU0360172 and RO0711401 have an interesting profile in acute and (sub)chronic pharmacological studies and produce a dose-dependent decrease of SWDs. Moreover, both compounds are effective in reducing SWDs in the cortex and thalamus. Interestingly, the GABA reuptake blocker tiagabine reduces SWDs in the cortex and not in the thalamus, while the efficacy of ethosuximide is higher in the cortex than in the thalamus. It is thought that VU0360172 stimulates cortex GABA interneurons, which inhibit highly excitable cortical neurons in the focal area. In the thalamus, VU0360172 most likely reduces tonic inhibition. Thus, group I mGlu receptor PAMs might be further developed as anti-absence drugs, with putative disease-modifying effects on epileptogenesis. The preclinical profile of group I mGlu receptor PAMS deserves to be further explored in models of generalized epilepsy and focal types of epilepsy