The "Twin Peaks" method of automated Spike-Wave detection: A two-step, two-criteria Matlab application.

Background: There are many automated spike-wave discharge detectors, but the known weaknesses of otherwise good methods and the varying working conditions of different research groups (mainly the access to hardware and software) invite further exploration into alternative approaches.

New Method: The algorithm combines two criteria, one in the time-domain and one in the frequency-domain, exploiting morphological asymmetry and the presence of harmonics, respectively. The time-domain criterion is additionally adjusted by normal modelling between the first and second iterations.

The Metabotropic Glutamate 5 Receptor in Sleep and Wakefulness: Focus on the Cortico-Thalamo-Cortical Oscillations.

Sleep is an essential innate but complex behaviour which is ubiquitous in the animal kingdom. Our knowledge of the distinct neural circuit mechanisms that regulate sleep and wake states in the brain are, however, still limited. It is therefore important to understand how these circuits operate during health and disease.

Network analysis reveals a role of the hippocampus in absence seizures: The effects of a cannabinoid agonist.

The role of the hippocampus (Hp) in absence epileptic networks and the effect of endocannabinoid system on this network remain enigmatic. Here, using adapted nonlinear Granger causality, we compared the differences in network strength in four intervals (baseline or interictal, preictal, ictal and postictal) in two hours before (Epoch 1) and six hours (epochs 2, 3 and 4) after the administration of three different doses of the endocannabinoid agonist WIN55,212-2 (WIN) or solvent. Local field potentials were recorded for eight hours in 23 WAG/Rij rats in the Frontal (FC), Parietal PC), Occipital Cortex (OC) and in the hippocampus (Hp).

Striatal Patchwork of D1-like and D2-like Receptors Binding Densities in Rats with Genetic Audiogenic and Absence Epilepsies.

Binding densities to dopamine D1-like and D2-like receptors (D1DR and D2DR) were studied in brain regions of animals with genetic generalized audiogenic (AGS) and/or absence (AbS) epilepsy (KM, WAG/Rij-AGS, and WAG/Rij rats, respectively) as compared to non-epileptic Wistar (WS) rats. Convulsive epilepsy (AGS) exerted a major effect on the striatal subregional binding densities for D1DR and D2DR. An increased binding density to D1DR was found in the dorsal striatal subregions of AGS-prone rats.

The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.

This review discusses the long-term effects of early-life environment on epileptogenesis, epilepsy, and neuropsychiatric comorbidities with an emphasis on the absence epilepsy. The WAG/Rij rat strain is a well-validated genetic model of absence epilepsy with mild depression-like (dysthymia) comorbidity. Although pathologic phenotype in WAG/Rij rats is genetically determined, convincing evidence presented in this review suggests that the absence epilepsy and depression-like comorbidity in WAG/Rij rats may be governed by early-life events, such as prenatal drug exposure, early-life stress, neonatal maternal separation, neonatal handling, maternal care, environmental enrichment, neonatal sensory impairments, neonatal tactile stimulation, and maternal diet.

Feasibility and potential of a bedside mini-EEG for diagnosing delirium superimposed on dementia.

Objective: Delirium superimposed on dementia (DSD) is difficult to diagnose because symptoms of delirium might be interpreted as symptoms of dementia. To improve diagnostic accuracy, we investigated the potential of a brief point-of-care EEG measurement.

Methods: Thirty older patients were included, all with Major Neurocognitive Disorder (i.

mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment of Absence Epilepsy: Preclinical and Human Genetics Data.

Background: Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for treating absence epilepsy. However, no information is available on mGlu3 receptors.

Objective: To examine whether (i) changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spikewave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy.

The prefrontal cortex shows widespread decrease in H3 histamine receptor binding densities in rats with genetic generalized epilepsies.

Distributions of brain H3 histamine receptors in regions of the prefrontal cortex were studied by assessing regional binding densities for [3 H](R)α-methylhistamine in coronal brain slices of normal rats and rats with genetically determined absence and/or audiogenic epilepsies. The three groups of epileptic rats displayed widespread significant decreases in H3 histamine receptor binding densities. A 20-25% decline was seen in the rostral aspects of the lateral prefrontal cortex, namely the granular, dysgranular, and dorsal agranular insular regions.

The role of thalamic nuclei in genetic generalized epilepsies.

There is no doubt on the participation of the thalamus in the various types of genetic generalized epilepsies as evidenced by multiple non-invasive imaging studies in humans as well as invasive studies in animal models of GGE. Based on human and mostly animal data gathered in early 2000 a so called 'three compartment model' on seizure generation was proposed conceptualizing the existence of a hyperexcitable cortical seizure onset zone providing excitation to relay cells of the relay thalamus and the inhibitory reticular thalamic nucleus (RTn). The interplay of corticothalamic excitation and feedforward inhibition via RTn is supposed to entrain thalamic relay neurons into synchronous, oscillatory activity for SWD sustainment.

The Orexin System: A Potential Player in the Pathophysiology of Absence Epilepsy.

Background: Absence epilepsy is characterized by the presence of spike-and-wave discharges (SWDs) at the EEG generated within the cortico-thalamo-cortical circuit. The molecular mechanisms involved in the pathophysiology of absence epilepsy are only partially known. WAG/Rij rats older than 2-3 months develop spontaneous SWDs, and they are sensitive to anti- absence medications.

Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning.

Seizure prediction is the grand challenge of epileptology. However, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long-lasting local field potential (LFP) recordings containing several hundred generalized spike and wave discharges (SWDs), acquired at eight locations in the cortico-thalamic system of absence epileptic rats, were iteratively analyzed in all possible combinations of either two or three recording sites, by a wavelet-based algorithm, calculating the product of the wavelet-energy signaling increases in synchronicity.

Thalamo-Cortical and Thalamo-Thalamic Coupling During Sleep and Wakefulness in Rats.

The thalamus, a heterogeneous brain structure, is involved in the generation of sleep-related thalamo-cortical oscillations. Higher order nuclei might possess a distinct function compared with first-order nuclei in brain communication. Here it is investigated whether this distinction can also be found during the process of falling asleep and deepening of slow-wave sleep.

An online platform and a dynamic database for neuropsychological assessment in Indonesia.

Proper use of neuropsychological tests in Indonesia is hindered by a lack of properly adapted neurocognitive tests as well as an absence of normative data. In 2016, we started adapting ten of these tests for use in Indonesia and collected data from healthy participants in Java. Here we introduce and propose a system that will facilitate the proper usage and interpretation of test scores: an online platform and a dynamic database.

Group I metabotropic glutamate receptor-mediated long term depression is disrupted in the hippocampus of WAG/Rij rats modelling absence epilepsy.

Absence epilepsy is frequently associated with cognitive dysfunction, although the underlying mechanisms are not well understood. Here we report that some forms of hippocampal synaptic plasticity are abnormal in symptomatic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Metabotropic Glu 1/5 receptor-mediated long term depression (LTD) at Schaffer collateral CA1 synapses is significantly reduced in symptomatic, 5-6 months old WAG/Rij rats compared to age-matched non epileptic control rats.

Dynamical mesoscale model of absence seizures in genetic models.

A mesoscale network model is proposed for the development of spike and wave discharges (SWDs) in the cortico-thalamo-cortical (C-T-C) circuit. It is based on experimental findings in two genetic models of childhood absence epilepsy-rats of WAG/Rij and GAERS strains. The model is organized hierarchically into two levels (brain structures and individual neurons) and composed of compartments for representation of somatosensory cortex, reticular and ventroposteriomedial thalamic nuclei.

Pharmacological activation of mGlu5 receptors with the positive allosteric modulator VU0360172, modulates thalamic GABAergic transmission.

Previous studies have shown that injection of the mGlu5 receptor positive allosteric modulator (PAM) VU0360172 into either the thalamus or somatosensory cortex markedly reduces the frequency of spike-and-wave discharges (SWDs) in the WAG/Rij model of absence epilepsy. Here we have investigated the effects of VU0360172 on GABA transport in the thalamus and somatosensory cortex, as possible modes of action underlying the suppression of SWDs. Systemic VU0360172 injections increase GABA uptake in thalamic synaptosomes from epileptic WAG/Rij rats.

Immediate versus late effects of vigabatrin on spike and wave discharges.

Vigabatrin increases GABA concentrations by inhibiting GABA transaminase. In previous studies, it was shown that vigabatrin increases the incidence of Spike and Wave Discharges (SWD) in the WAG/Rij rat model for absence epilepsy. Since following a single dose of vigabatrin GABA concentrations are known to be increased for several days, the present study sheds light on how the previously described changes in SWD characteristics develop over a longer time frame.

Circadian Rhythms and Epilepsy: A Suitable Case for Absence Epilepsy.

Many physiological processes such as sleep, hormonal secretion, or thermoregulation, are expressed as daily rhythms orchestrated by the circadian timing system. A powerful internal clock mechanism ensures proper synchronization of vital functions within an organism on the one hand, and between the organism and the external environment on the other. Some of the pathological processes developing in the brain and body are subjected to circadian modulation as well.

Establishing Drug Effects on Electrocorticographic Activity in a Genetic Absence Epilepsy Model: Advances and Pitfalls.

The genetic rat models such as rats of the WAG/Rij strain and GAERS were developed as models for generalized genetic epilepsy and in particular for childhood absence epilepsy. These animal models were described in the eighties of the previous century and both models have, among others, face, construct and predictive validity. Both models were and are currently used as models to predict the action of antiepileptic medication and other experimental treatments, to elucidate neurobiological mechanisms of spike-wave discharges and epileptogenesis.

Altered SWD stopping mechanism in WAG/Rij rats subchronically treated with the cannabinoid agonist R(+)WIN55,212-2.

A single injection of the cannabinoid agonist R(+)WIN55,212-2 (WIN) is known to cause an increase of the mean duration of spontaneously occurring spike-and-wave discharges (SWDs) in rats of the WAG/Rij strain, a genetic model for absence epilepsy. The aim of the present study was to establish whether repeated activation of CB receptors with WIN leads to tolerance in its effect on SWD parameters, spectral density, and behavior over time. Adult male WAG/Rij rats (n = 16) were treated with WIN (6 mg/kg) or vehicle (olive oil).

Neonatal exposure to AY-9944 increases typical spike and wave discharges in WAG/Rij and Wistar rats.

Absence-epileptic seizures appear in the EEG as Spike and Wave Discharges (SWDs). Typical SWDs develop spontaneously in WAG/Rij rats, an inbred Wistar strain. Atypical SWDs however were reported in studies in which the cholesterol synthesis inhibitor AY-9944 was administered to neonatal Wistar rats, causing absence-like seizures later in life.

A network approach to investigate the bi-hemispheric synchrony in absence epilepsy.

Objective: Our objective was to unravel the dynamics underlying spike-and-wave discharges (SWDs) characteristic for childhood absence epilepsy.

Methods: SWDs were recorded for a cohort of 28 children using magnetoencephalography. Non-linear association analyses and a graph theoretical metric of local connectedness (LoC) were utilized in a sliding window starting one s before till four s after ictal onset.