Publications by authors named "G van Luijtelaar"

162 Publications

Seizure prediction in genetic rat models of absence epilepsy: improved performance through multiple-site cortico-thalamic recordings combined with machine learning.

eNeuro 2021 Nov 12. Epub 2021 Nov 12.

Institute of Physiology I, University of Münster, Münster, Germany

Seizure prediction is the grand challenge of epileptology. Yet, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long lasting 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. Sensitivity and false alarm rate of prediction were compared between various combinations and wavelet spectra of true- and false positive predictions were fed to a random forest machine learning algorithm to further differentiate between them. Wavelet analysis of intracortical and cortico-thalamic LFP traces showed a significantly smaller number of false alarms compared intrathalamic combinations, while predictions based on recordings in layer 4, 5 and 6 of the somatosensory-cortex significantly outreached all other combinations in terms of prediction sensitivity. In 24-hours out-of-sample recordings of 9 GAERS, containing diurnal fluctuations of SWD occurrence, classification of true and false positives by the trained random forest further reduced the false alarm rate by 71%, although at some tradeoff between false alarms and sensitivity of prediction, as reflected in relatively low F1-score values. Results provide support for the cortical-focus theory of absence epilepsy and allow the conclusion that SWDs are predictable to some degree. The latter paves the way for the development of closed-loop SWD prediction-prevention systems. Suggestions for a possible translation to human data are outlined.Seizure prediction was declared the grand challenge of epileptology. While most effort was devoted to the prediction of focal seizures, generalized seizures were regarded as stochastic events. Results of this study demonstrate that above chance prediction of generalized spike and wave discharges (SWDs) is possible in long lasting, pseudoprospective 24 hours recordings of absence epileptic rats, by means of wavelet analysis of LFP traces acquired near the proposed cortical initiation network in S1 and further classification of true and false positive detections by a trained random forest machine learning algorithm. Moreover, as lower SWD prediction performance was achieved by analysis of LFP traces distant to S1, the study provides evidence supporting the cortical focus theory of absence epilepsy.
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http://dx.doi.org/10.1523/ENEURO.0160-21.2021DOI Listing
November 2021

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

Brain Connect 2021 Oct 22. Epub 2021 Oct 22.

Institute of Physiology I, University of Münster, Münster, Germany.

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. A nonlinear version of Granger causality was used to describe changes in directed network activity between the somatosensory cortex and rostral reticular thalamic nucleus (rRTN) and caudal reticular thalamic nucleus (cRTN), the higher order posterior (PO)- and anterior-thalamic nuclei (ATN), and the first-order ventral posteromedial thalamic nucleus (VPM) as assessed in local field potential recordings acquired during passive wakefulness (PW), light slow-wave sleep (LSWS), and deep slow-wave sleep (DSWS) in freely behaving rats. Surrogate statistics was used to assess significance. Decreases in cortico-thalamo-cortical couplings were found. In contrast, multiple increases in intrathalamic couplings were observed. In particular, the rRTN increased its inhibition on the ATN from PW to LSWS, and this was further strengthened from LSWS to DSWS. The cRTN increased its coupling to VPM and PO from PW to LSWS, but the coupling from cRTN to VPM weakened at the transition from LSWS to DSWS, while its coupling to PO strengthened. Furthermore, intra-RTN coupling from PW to LSWS was differently changed compared with the change from LSWS to DSWS. It can be inferred that higher order (ATN and PO) and first-order nuclei (VPM) are differentially inhibited during DSWS, which might be relevant for a proper functioning of sleep-related processes.
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http://dx.doi.org/10.1089/brain.2021.0052DOI Listing
October 2021

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

Appl Neuropsychol Adult 2021 Jul 13:1-10. Epub 2021 Jul 13.

Psychology Faculty, Soegijapranata Catholic University, Semarang, 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. Newly collected data (492 healthy adults) of the Indonesian version of the Boston Naming Test (I-BNT) were used to illustrate the usefulness of the two functions. Analysis of variances, post-hoc tests, and a simulation study revealed the effects of age and education on the I-BNT, indicating that it is imperative to fine-tune the reference group based on these demographic factors. Putative inadequate sample size issues for obtaining reliable normative scores were overcome by employing regression analyses and the prediction of normative scores. It can be concluded that a flexible online platform is available for the calculation of normative scores either based on the whole population, on fine-tuned reference groups, or on predicted scores. The dynamic database's growth will allow to obtain even more fine-tuned and more reliable reference data as well as more accurate predictions. Fine-tuned reference data are badly needed for the heterogenous Indonesian population.
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http://dx.doi.org/10.1080/23279095.2021.1943397DOI Listing
July 2021

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

Neuropharmacology 2021 09 29;196:108686. Epub 2021 Jun 29.

School of Life Sciences, University of Warwick, Coventry, UK. Electronic address:

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. There were no significant changes in mGlu1/5-dependent LTD in pre-symptomatic, 4-6 weeks old WAG/Rij rats compared to age matched controls. The changes in LTD found in symptomatic WAG/Rij forms are not indicative of general deficits in all forms of synaptic plasticity as long term potentiation (LTP) was unchanged. Immunoblot analysis of hippocampal tissue showed a significant reduction in mGlu5 receptor expression, a trend to an increase in pan Homer protein levels and a decrease in GluA1 receptor expression in the hippocampus of symptomatic WAG/Rij rats vs non-epileptic control rats. There were no changes in mGlu1α receptor or GluA2 protein levels. These findings suggest that abnormalities in hippocampal mGlu5 receptor-dependent synaptic plasticity are associated with the pathological phenotype of WAG/Rij rats. This lays the groundwork for the study of mGlu5 receptors as a candidate drug target for the treatment of cognitive dysfunction linked to absence epilepsy.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108686DOI Listing
September 2021

Dynamical mesoscale model of absence seizures in genetic models.

PLoS One 2020 29;15(9):e0239125. Epub 2020 Sep 29.

Saratov Branch of Kotel'nokov Institute of Radioengineering and Electronics of Russian Academy of Sciences, Saratov, Russia.

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. The cortex and the two thalamic compartments contain excitatory and inhibitory connections between four populations of neurons. Two connected subnetworks both including relevant parts of a C-T-C network responsible for SWD generation are modelled: a smaller subnetwork for the focal area in which the SWD generation can take place, and a larger subnetwork for surrounding areas which can be only passively involved into SWDs, but which is mostly responsible for normal brain activity. This assumption allows modeling of both normal and SWD activity as a dynamical system (no noise is necessary), providing reproducibility of results and allowing future analysis by means of theory of dynamical system theories. The model is able to reproduce most time-frequency changes in EEG activity accompanying the transition from normal to epileptiform activity and back. Three different mechanisms of SWD initiation reported previously in experimental studies were successfully reproduced in the model. The model incorporates also a separate mechanism for the maintenance of SWDs based on coupling analysis from experimental data. Finally, the model reproduces the possibility to stop ongoing SWDs with high frequency electrical stimulation, as described in the literature.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239125PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524004PMC
November 2020
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