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Indonesia lacks standardized and adapted neuropsychological tests, which hampers their use in clinical practice. Recently, an Indonesian Neuropsychological Consortium has initiated the adaptation of ten internationally commonly used tests for use in Indonesia. Here, we report the analyses of the psychometric properties, including preliminary normative data, the reliability, the underlying cognitive constructs, and the effects of age and education on these constructs as validity indicators.Four hundred ninety healthy adults living on Java Island participated in this study. All subjects completed the Indonesian Neuropsychological Test Battery (INTB) for diagnosis of various cognitive functions. The test-retest reliability was determined in a parallel study with fifty participants.Underlying cognitive constructs were assessed with Principal Component Analysis (PCA) revealed seven constructs that accounted for 62.84% of the total variance, and the goodness of fit of the model was good. ANOVAs showed significant effects of age on six constructs (i.e., speed of visuospatial information processing, auditory short-term and working memory, speed and inhibitory control, and verbal learning ability). Age effects were not found for executive internal language. All constructs showed effects of education, except for recall and verbal learning ability.Interestingly, as expected, not all constructs showed the same age-dependent decline, and if present, all seem to be unique. It is concluded that the psychometric properties of the INTB justify their usage for the Indonesian population.

Burnout is commonly measured with the Maslach Burnout Inventory (MBI), which consists of three subscales measuring emotional exhaustion, personal accomplishment, and cynicism. We adapted the scale and then explored and confirmed the three dimensions on the Indonesian version named The Maslach-Trisni Burnout Inventory (M-TBI) with an exploratory analysis followed by Confirmatory Factor Analysis (CFA) from 822 workforces. The sensitivity for different job characteristics and demographic factors was established with analyses of variance and based on percentile scores of the subscales, three categories for burnout tendency were proposed. The scores on the three subscales were compared with those of Western countries. There are similar scores for emotional exhaustion and cynicism, but the sample score for personal accomplishment tends to be lower than the western countries. It can be concluded that the M-TBI scale is a reliable, sensitive, and efficient tool to measure the burnout tendency in the workforce in Indonesia.

Contains fulltext : 285519.pdf (Publisher’s version ) (Open Access) The performance of cognitive tests is highly dependent on the proficiency of the language in which the tests are administered. Not all Indonesians speak Indonesian daily and many are bilingual. We investigate whether language(s) spoken affects the performance on three language tests in 840 participants ranging in age (16-80) and education (6-22 years). Analysis of covariance followed by Helmert contrasts showed a disadvantage on the Boston Naming Test (BNT) and on the most difficult items of the Token Test for those who do not speak Bahasa daily. Bilinguals did worse on the BNT. Education had a large positive effect on the language tests, age a smaller negative effect. This suggests that besides age and education, the factor of language spoken, either in public or at home, needs to be taken into account when a participant's test scores on the BNT and TT are interpreted and compared with normative data. 12 p.

Item does not contain fulltext 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). The four intervals were visually marked by an expert neurophysiologist and the strength of couplings between electrode pairs were calculated in both directions. Ictally, a strong decrease in coupling strength was found between Hp and FC, as well as a large increase bidirectionally between PC and FC and unidirectionally from FC and PC to OC, and from FC to Hp over all epochs. The highest dose of WIN increased the couplings strength from FC to Hp and from OC to PC during 4 and 2 hr respectively in all intervals, and decreased the FC to PC coupling strength postictally in epoch 2. A single rat showed generalized convulsive seizures after the highest dose: this rat shared not only coupling changes with the other rats in the same condition, but showed many more. WIN reduced SWD number in epoch 2 and 3, their mean duration increased in epochs 3 and 4. Conclusions:during SWDs FC and PC are strongly coupled and drive OC, while at the same time the influence of Hp to FC is diminished. The first is in agreement with the cortical focus theory, the latter demonstrates an involvement of the hippocampus in SWD occurrence and that ictally the hippocampal control of the cortico-thalamo-cortical system is lost. WIN causes dramatic network changes which have major consequences for the decrease of SWDs, the occurrence of convulsive seizures, and the normal cortico-cortical and cortico-hippocampal interactions. 10 p.

Contains fulltext : 235093.pdf (Publisher’s version ) (Open Access) 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. 10 p.

Contains fulltext : 236666.pdf (Publisher’s version ) (Open Access) Changes from traditional face-to-face to internet-delivered psychological assessment are urgently needed given the long-lasting pandemic, the general need for fast and efficient tests and test procedures, and easier availability and access for test-takers in remote settings. We used a quasi-experimental non-randomized group design for the comparison of two word fluency test procedures: one traditional that is face-to-face (n = 30) and one supervised via internet (n = 30). Participants were 17-31 years, education level high school and Bachelor. The letters S, K, T were used for the phonemic fluency test, for the emotion word fluency test subjects had to generate words related to subjective emotional feelings or the expression of emotions. The results showed that traditional administered and internet-delivered testing are equivalent (our hypothesis) as seen from the absence of significant differences between the two groups in the performances of all four word fluency tests (p > .05) and small effect sizes (Cohen's d range < .5). Significant correlations were found between the fluency tasks, irrespective of the way of test administration (p < .05). It can be concluded that the word fluency tasks can be assessed by supervised internet-delivered testing, but this is limited to a sample of young adults. 15 p.

Contains fulltext : 237073.pdf (Publisher’s version ) (Closed access) Introduction: 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 to 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. Methods: A non-linear version of Granger-Causality was used to describe changes in directed network activity between somatosensory-cortex and rostral and caudal reticular-thalamic-nucleus, the higher-order posterior- and anterior- thalamic nuclei and the first-order ventral-postero-medial thalamic nucleus as assessed in LFP recordings acquired during passive-wakefulness (PW), light and deep slow-wave sleep (LSWS, DSWS) in freely behaving rats. Surrogate statistics were used to assess significance. Results: Decreases in cortico-thalamo-cortical couplings were found. In contrast, multiple increases in intrathalamic couplings were observed. In particular, the rostral reticular-thalamic-nucleus (rRTN) increased its inhibition on the anterior (ATN) from PW to LSWS, and this was further strengthened from LSWS to DSWS. The caudal reticular-thalamic-nucleus (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 to the change from LSWS to DSWS. Discussion: 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. 10 p.

Item does not contain fulltext 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. Results: A focal pattern of bilateral frontal and parietal areas with high LoC during the spikes alternated by generalized patterns during the waves was found for all children studied during generalization of the SWDs. In the interval preceding the generalization a focal parietal region was most often (16/28) encountered and less often an occipital (4/28), temporal (5/28) or frontal (3/28) region. 55% of the children with a parietal/occipital focal onset became seizure free after the administration of two anti-epileptic drugs, and only 12.5% with a temporal/frontal focal onset. Conclusions: The transition from interictal to the ictal state is for some of the children characterized by dominant LoC at either the parietal/occipital and for others at the frontal/temporal region. Significance: The focal onset of the SWDs varies in location among the children with a clinical similar profile, who, however, seemingly are differing with regard to seizure control. 9 p.

Contains fulltext : 202738.pdf (Publisher’s version ) (Open Access) Sensory information processing and higher cognitive functions rely on the interactions between thalamus and cortex. Many types of neurological and psychiatric disorders are accompanied or driven by alterations in the brain connectivity. In the present study putative changes in functional and effective cortico-cortical (CC), thalamo-cortical (TC) and cortico-thalamic (CT) connectivity during wakefulness and slow-wave sleep in a model of thalamo-cortical dysrhythmia (TCD), TRIP8b-/- mice and in control (WT) mice are described. Coherence and nonlinear Granger Causality (GC) were calculated for twenty 10 s length epochs of slow-wave sleep and active-wakefulness of each animal. Coherence was reduced between 4 and ca 20 Hz in the cortex and between cortex and thalamus during slow-wave sleep compared to active-wakefulness in WT, but not in TRIP8b-/- mice. Moreover, TRIP8b-/- mice showed lower CT coherence during active-wakefulness compared to WT mice; these differences were no longer present during slow-wave sleep. Unconditional GC analysis also showed sleep related reductions in TC and CT couplings in WT mice, while TRIP8b-/- mice showed diminished wake and enhanced sleep CC coupling and rather strong CT directed coupling during wake and sleep, albeit smaller during sleep. Conditional GC coupling analysis confirmed the diminished CC and enhanced CT coupling in TRIP8b-/- mice. Our findings indicate that altered properties of HCN channels, characterizing TRIP8b-/- mice, have clear effects on CC, TC and CT networks. A more complete understanding of the function of the altered communication within these networks awaits detailed phenotyping of TRIP8b-/- mice aimed at specifics of sensory and attentional processes. 12 p.

Contains fulltext : 235294.pdf (Publisher’s version ) (Closed access) 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. 12 p.

Item does not contain fulltext Albino rats have a higher amplitude of the late complex of the flash-induced visual evoked potential (VEPs) and afterdischarges (AD), the latter in particular during low states of arousal and vigilance than hooded and pigmented rats. These ADs are generated in cortico-geniculate-cortical pathways and have been used as a model for the evaluation of putative anti-absence drugs, while properties of flash-evoked VEPs were also used to predict toxic effects of new compounds, including putative anticonvulsant drugs. Flash VEPs made during spike-wave discharges (SWDs) in the genetic animal absence models have revealed that their sensory system is largely intact; interestingly the state of the brain during SWDs mimics that of slow-wave sleep. Photic stimulation in the genetic epileptic models does not provoke a photoparoxysmal response, as has been found in some absence epilepsy patients. However, trains of intense photic stimulation was efficacious in inducing neuroplastic changes leading to photoparoxysmal activity in normal young adult Sprague-Dawley rats. SWDs originating from the somatosensory cortex in the genetic rat models were reduced during photic stimulation due to enhanced arousal. Moreover, outcomes from fMRI studies in absence patients showed that the pathways and the brain regions involved in the occurrence of spontaneous occurring SWDs differ from those involved in the SWDs elicited by photic stimulation. Although both SWDs and flash-evoked AD are cortico-thalamo-cortical oscillations, it seems that there are important differences between the rodent absence models, regarding the brain networks and mechanisms and humans with absence seizures between physiological elicited photically induced ADs and the spontaneous occurring pathological SWDs.

Contains fulltext : 214178.pdf (Publisher’s version ) (Open Access) 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 CB1 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 (6mg/kg) or vehicle (olive oil). Injections (s.c.) took place 3 times per week during 2weeks. Electroencephalogram (EEG) recordings, each lasting 24h, were made 3 times: immediately before the first injection (baseline), immediately after the first injection (acute treatment), and after 2weeks of treatment (subchronic treatment). The recordings were analyzed regarding incidence, durations of SWDs, and hazard rates of the durations of SWDs, the latter to describe SWD stopping probabilities. Putative changes in the spectral content of the EEG before and after WIN during active and passive behaviors were additionally investigated. Spike-and-wave discharge incidence was not affected by the acute and subchronic treatments. The mean duration of the SWDs was significantly longer than controls in the acute WIN-treated animals [11.9-s standard error of the mean (SEM): 0.64 compared with 8.4-s SEM: 0.25] as well as in subchronically treated animals (11.5-s SEM: 1.00 compared with 8.4-s SEM: 0.25). Hazard rates were significantly lower for WIN-treated animals at SWD durations in the 5.04-20.16-s range on both occasions. No effects of WIN on the frequency spectrum of the ongoing EEG were found, neither acutely nor after repeated administration. Evidence for tolerance was not found. The results on the mean duration and hazard rates suggest that stimulating the endocannabinoid system affects the SWD stopping mechanism, resulting in more long SWDs. We speculate that this effect is likely to be a direct result of CB1 receptor agonism and a subsequent decrease in the availability of gamma-aminobutyric acid (GABA) in the reticular thalamic nucleus, which further weakens, in WAG/Rij rats already disturbed, the stopping mechanism of the SWDs. 10 p.

Contains fulltext : 217713.pdf (Publisher’s version ) (Closed access) 30% of epileptic patients are resistant to drug therapy. A prospective treatment strategy for refractory epilepsy patients is a brain-computer interface (BCI) in which the epileptic seizures are modulated either by the preprogrammed stimulation schedules (open loop) or via the closed-loop stimulation. The closed-loop BCI implies that seizures are automatically detected and that the detection triggers stimulation which subsequently aborts seizures. Up to now, this experimental treatment is only able to reduce seizures duration, while the ultimate aim is their complete abolishment. We have developed a closed-loop BCI aimed to predict and prevent spike-wave discharges, the electrophysiological anchor of absence seizures, in a genetic absence rat model; it predicted 45% of the seizures while the remaining ones were detected. When we evaluated the combination of the prediction and seizure detection with closed-loop electrical stimulation, a 72% decrease of seizure activity duration was achieved. The 8th International Winter Conference on Brain-Computer Interface (BCI) (Gangwon, Korea (South), 26-28 Feb. 2020)

Contains fulltext : 219351.pdf (Publisher’s version ) (Open Access) 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. To achieve this, we injected adult WAG/Rij rats with 500 mg/kg and recorded their EEG for 48 hours. SWD were quantified, and their peak frequencies were calculated. Our results showed three rapid onset effects: a sharp increase in SWD incidence, from 12.5 /hour to 133/hour), this increase lasted only 4.4 hours, an increase in mean SWD duration, from 4.6 s to 8.1 s and a drop in peak frequency, from 8 to 6 Hz. Since it takes several hours before GABA concentrations are sufficiently increased, we propose that these immediate effects are caused by direct stimulation of both GABAA and GABAB receptors by the molecule vigabatrin. Next, the mean SWD duration decreased below baseline values after 4.4 hours. Hazard rate analysis showed that this is caused by an increased probability of short SWD. We argue that these changes are caused by increased activation of both GABAA and GABAB receptors in the frontal cortex and the thalamus, and more specifically, in the Reticular Thalamic Nucleus (RTN). After approximately 34 hours, the probability of short SWD returned to normal. This suggests the occurrence of downregulation of GABA receptors. The decrease in peak frequency was still present 48 hours after injection. It has been argued that the balance between GABAA and GABAB receptor-mediated activity in the RTN is crucial for controlling this SWD characteristic. It can be concluded that a single dose of vigabatrin results in remarkable and opposite effects over time: an initial, proabsence effect is followed by an antiabsence effect. 10 p.

Contains fulltext : 221388.pdf (Publisher’s version ) (Closed access) Contains fulltext : 221388pre.pdf (Author’s version preprint ) (Open Access) 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. Consistent with this observation, VU0360172 could also enhance thalamic GAT-1 protein expression, depending on the dosing regimen. This increase in GAT-1 expression was also observed in the thalamus from non-epileptic rats (presymptomatic WAG/Rij and Wistar) and appeared to occur selectively in neurons. The tonic GABAA receptor current present in ventrobasal thalamocortical neurons was significantly reduced by VU0360172 consistent with changes in GAT-1 and GABA uptake. The in vivo effects of VU0360172 (reduction in tonic GABA current and increase in GAT-1 expression) could be reproduced in vitro by treating thalamic slices with VU0360172 for at least 1 h and appeared to be dependent on the activation of PLC. Thus, the effects of VU0360172 do not require an intact thalamocortical circuit. In the somatosensory cortex, VU0360172 reduced GABA uptake but did not cause significant changes in GAT-1 protein levels. These findings reveal a novel mechanism of regulation mediated by mGlu5 receptors, which could underlie the powerful anti-absence effect of mGlu5 receptor enhancers in animal models. 11 p.

Contains fulltext : 218080.pdf (Publisher’s version ) (Open Access) 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. Although the electroencephalagram (EEG)/electrocorticogram (ECoG) is imperative for establishing absence seizures and to quantify the for absence epilepsy typical spike-wave discharges, monitoring the animals behavior is equally necessary. Here an overview is given regarding the design of drug evaluation studies, which animals to use, classical and new EEG variables, the monitoring and quantification of the behavior of the rats, some pitfalls regarding the interpretation of the data, and some developments in EEG technology. 12 p.

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.Significance statementSeizure 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.

Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b−/−). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K+ current, I A, in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5–4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings. Electronic supplementary material The online version of this article (10.1007/s00429-017-1559-z) contains supplementary material, which is available to authorized users.

Contains fulltext : 178408.pdf (Publisher’s version ) (Open Access) Sleep spindles are phasic bursts of thalamo-cortical activity, visible in the cortex as transient oscillations in the sigma range (usually defined in humans as 12-14 or 9-16 Hz). They have been associated with sleep-dependent memory consolidation and sleep stability in humans and rodents. Occurrence, frequency, amplitude and duration of sleep spindles co-vary with age, sex and psychiatric conditions. Spindle analogue activity in dogs has been qualitatively described, but never quantified and related to function. In the present study we used an adjusted version of a detection method previously validated in children to test whether detections in the dogs show equivalent functional correlates as described in the human literature. We found that the density of EEG transients in the 9-16 Hz range during non-REM sleep relates to memory and is characterized by sexual dimorphism similarly as in humans. The number of transients/minute was larger in the learning condition and for female dogs, and correlated with the increase of performance during recall. It can be concluded that in dogs, automatic detections in the 9-16 Hz range, in particular the slow variant (

Contains fulltext : 219607.pdf (Publisher’s version ) (Closed access) 2 p.

Item does not contain fulltext 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. Atypical SWDs seemed to differ from typical SWDs in 3 aspects: lower peak frequency, longer duration, and involvement of the hippocampus. The aim of the present study was to investigate the effect of AY-9944 on typical SWDs. Male Wistar and WAG/Rij rats were injected with 7.5 mg/kg AY-9944 or saline postnatally. After 6 months, EEGs were recorded from the cortex and the hippocampus. Incidence, duration and peak frequency of the SWDs were determined. The SWD stopping probability was estimated by hazard rate analysis. Hippocampal involvement was assessed by cross correlation analysis of the hippocampus and cortex channels. The Wistar rats unexpectedly showed a high incidence of spontaneous SWDs. The AY-treatment increased the total SWD duration in both Wistar and WAG/Rij rats: the incidence was 1.6 times higher and the mean SWD duration was 1.4 times longer than in the saline-treated rats. The peak frequency of the SWDs did not change. The hazard rates were lower in the AY-treated rats, so some very long SWDs were observed. Cross correlations of spiky activity in the hippocampus pointed to volume conduction rather than to genuine SWD activity in this area. In summary, we found no indication that SWDs in AY-treated animals differ from typical SWDs. However, since saline-treated rats had many spontaneous SWDs, other rat strains might respond differently. With respect to the mechanism, the appearance of long SWDs suggests that the SWD stopping mechanism is affected by the treatment. We speculate that this effect is due to changes in the distribution of GABA-ergic and glutamatergic receptors in lipid rafts. 9 p.

Contains fulltext : 203447.pdf (Publisher’s version ) (Open Access) Rapid changes in the light-dark cycle cause circadian desynchronization between rhythms of spike-wave discharges (SWDs) and motor activity in genetic epileptic rats, and this is accompanied by an increase in epileptic activity. Given the close relationship between absence seizures and sleep-wake states, the present study assessed firstly a putative relationship between vigilance rhythms and SWDs during re-synchronization, and secondly sleep-wake patterns responsible for increased epileptic activity. Lastly, in a view of existing evidence that melatonin and its agonists accelerate re-synchronization, the effects of agomelatine upon the speed of re-synchronization of different sleep-wake states and SWDs were investigated. Simultaneous electroencephalographic and electromyographic recordings were made in symptomatic WAG/Rij rats, before, during and 10 days following an 8 h light phase delay. Agomelatine was orally administered acutely and sub-chronically, during 10 post-shift days. The magnitude of the advance after the shift and the speed of re-synchronization were specific for various rhythms. Most prominent change was the increase in REM sleep duration during the dark phase. A post-shift increase in passive wakefulness and a reduction in deep slow-wave sleep coincided with an aggravation of SWDs during the light phase. Agomelatine showed neither an effect on sleep-wake parameters and SWDs, nor affected re-synchronization. The same speed of re-synchronization of SWDs and light slow-wave sleep suggests that both are controlled by a common circadian mechanism. The redistribution of SWDs and their increase in the light phase after the shift may be of importance for patients with absence epilepsy planning long trans-meridian flight across time zones. 12 p.

Contains fulltext : 201991.pdf (Publisher’s version ) (Open Access) Introduction: Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors. These receptors mediate fast excitatory synaptic transmission in the central nervous system (CNS) and their blockade may cause severe adverse effects such as sedation, cognitive impairment and psychotomimetic effects. Metabotropic glutamate (mGlu) receptors are more promising drug targets because these receptors modulate synaptic transmission rather than mediate it. Areas covered: We review the current evidence that links mGlu receptor subtypes to the pathophysiology and experimental treatment of convulsive and absence seizures. Expert Opinion: While mGlu5 receptor negative allosteric modulators have the potential to be protective against convulsive seizures and hyperactivity-induced neurodegeneration, drugs that enhance mGlu5 and mGlu7 receptor function may have beneficial effects in the treatment of absence epilepsy. Evidence related to the other mGlu receptor subtypes is more fragmentary; further investigations are required for an improved understanding of their role in the generation and propagation of seizures. 11 p.

Contains fulltext : 160644.pdf (Publisher’s version ) (Closed access) Introduction: The purpose of this preliminary clinical trial was to investigate whether acupuncture has a positive influence on sleep and symptomatology in patients with schizophrenia or depression. Methods: A randomized controlled trial was used. One hundred participants were recruited: 40 outpatients with schizophrenia, 40 with depression, and 20 healthy controls. They all filled in a depression inventory, and the positive and negative symptoms of the patients with schizophrenia were evaluated by their psychiatrists. All participants were asked to complete a sleep log for two weeks. For the psychiatric patients, a randomized design with experimental (three months of acupuncture treatment) and control (waitlist) conditions was used, after which all measurements were conducted once more. Results: Before treatment, patients with depression were awake longer during the night, needed more time to fall asleep, evaluated their sleep as less relaxed, felt more exhausted, and reported a lower average performance level than healthy controls did. Moreover, patients with depression slept shorter and felt more exhausted than patients with schizophrenia. Patients with schizophrenia solely reported a lower average performance level compared to healthy controls. Acupuncture slightly improved sleep and depressive symptoms in patients with depression, but did not affect sleep nor influence positive and negative symptoms in patients with schizophrenia. Conclusion: These preliminary data suggest that acupuncture can be used in order to reduce symptoms and improve sleep to some extent in patients with depression, but as a result of the lack of comparative data, it is impossible to reliably say anything about its effects for patients with schizophrenia. 8 p.

Ethosuximide (ETX) has become the drug of choice in the treatment of patients with absence seizures taking into account both its efficacy, tolerability and antiepileptogenic properties. However, 47% of subjects treated with ETX failed in therapy, and most antiepileptic drugs have cognitive side effects. VU0360172, a positive allosteric modulator (PAM) of mGluR5, acutely and chronically administered decreased seizures dose dependently in rats of the WAG/Rij strain, a genetic absence model. Here it is investigated whether anti-epileptogenesis induced by ETX alters the sensitivity of VU0360172 as an anti-absence drug, and cognition is affected during and after chronic ETX treatment. Method: Male WAG/Rij rats were chronically treated with ETX for 4 months. EEG’s were recorded during and after treatment as well as challenged with VU0360172. Rats were also periodically exposed to a cue discrimination learning task in a Y-maze. mGlu5 receptors were quantified with Western Blot. Results: Antiepileptogenesis was successfully induced by ETX and VU0360172 showed a time and dose dependent anti-absence action. However, chronic ETX treated rats showed a decrease in absences both during and after the end treatment, without clear time and dose related effects. The decrease of sensitivity for VU0360172 was not accompanied by a change in mGluR5 expression in cortex and thalamus. Chronic ETX enhanced motivation to collect sucrose pallets and this was followed by an increase in cued discrimination learning. It is concluded that VU0360172 keeps its antiabsence effects after chronic treatment. Moreover, its differential effects in the two groups cannot be explained by a simple receptor down regulation suggesting a more downstream interaction between ETX and mGluR5. The cognitive enhancing effects of ETX, as found at the end of the experiment might be mediated to the antidepressant action of ETX as expressed by an increase in the rewarding properties of sucrose pallets.

Contains fulltext : 200825.pdf (Publisher’s version ) (Open Access) Objective: The putative neuroprotective and disease-modifying effects of lamotrigine (LTG) and ethosuximide (ESM) were investigated in the lithium-pilocarpine (Li-Pc) model of temporal-lobe epilepsy (TLE) in rats. Then, spontaneous recurrent seizures (SRS), neuronal loss and astrogliosis were assessed. Methods: Status Epilepticus (SE) was induced by Li-Pc in five experimental groups: 24 h after SE, all rats received twice daily either a low (10 mg/kg) or high (20 mg/kg) dose of LTG, or a low (25 mg/kg) or high (50 mg/kg) dose of ESM, or solvent. The sixth group (control) did not receive Li-Pc and was given twice daily injections with solvent only. Drug administration lasted for 7 d. Rats were systematically observed in the 5th and 6th weeks, after that the brains were prepared for histology. Results: LTG dose-dependently decreased the frequency of SRS, and restricted neuronal loss, as well as astrogliosis in the hippocampus compared with the untreated SE control group. However, ESM had none of the above-mentioned effects. Conclusion: LTG had protective as well as disease-modifying effects in this TLE model. It was revealed that the disease-modifying effects were accompanied by the prevention of neuronal loss and astrogliosis. ESM was devoid of antiepileptogenic and its accompanying histological effects in this TLE model, in contrast to the antiepileptogenic effects found in the genetic absence epilepsy models, suggesting that different mechanisms are involved in the different models for epileptogenesis and antiepileptogenesis. 6 p.