Epileptic Discharges Research Articles

Effects of inverse methods and spike phases on interictal high-density EEG source reconstruction

ObjectiveTo determine the effect of inverse methods and timepoints of interictal epileptic discharges (IEDs) used for high-density electric source imaging (hd-ESI) in pharmacoresistant focal epilepsies. MethodsWe retrospectively evaluated the hd-ESI and [18F]fluorodeoxyglucose positron emission tomography (18FDG-PET) of 21 operated patients with pharmacoresistant focal epilepsy (Engel I). Volumetric hd-ESI was performed with three different inverse methods such as the inverse solution linearly constrained minimum variance (LCMV, a beamformer method), standardized low resolution electromagnetic tomography (sLORETA) and weighted minimum-norm estimation (wMNE) and at different IED phases. Hd-ESI accuracy was determined by volumetric overlap and distance between hd-ESI source maximum, as well as 18FDG-PET hypometabolic region relative to the resection zone (RZ). ResultsIn our cohort, the shortest distances and greatest volumetric overlaps to the RZ were found in the half-rise and peak-phase for all inverse methods. The distance to the RZ was not different between the centroid of the clinical hypothesis-based cluster and the source maximum in peak-phase. However, the distance of the hypothesis-based cluster was significantly shorter compared to the cluster selected by the smallest p-value. ConclusionsHd-ESI provides the greatest accuracy in determining the RZ at the IED half-rise and peak-phase for all applied inverse methods, whereby sLORETA and LCMV were equally accurate. SignificanceOur results offer guidance in selecting inverse methods and IED phases for hd-ESI, compare the performance of hd-ESI and 18FDG-PET and encourage future studies in investigating the relationship between interictal ESI and 18FDG-PET hypometabolism.

Our experience of pediatric epilepsy surgery

Objective: to evaluate the effectiveness and safety of different operations in children with drug-resistant epilepsy. Materials and Method. 91 children with drug-resistant epilepsy were enrolled in a retrospective study. Mean age was 10.3±5.1 years. Anterior temporal lobectomy was performed in 16 (57.1%) patients, lesionectomy – in 9 (10.0%), microsurgical callosotomy in 18 (19.8%), stereotactic callosotomy in 7 (7.7%), multifocal resections in 4 (4.4%), functional hemispherotomy in 14 (15.6%). Stereotactic radiofrequency callosotomy was performed on a CRW Stereotactic frame (Radionics Inc., USA). Ultrasound navigation and neuronavigation were used in 6 (7%) and 14 (15%) cases correspondingly. Intraoperative corticography was applied in 8 (9%) cases. Postoperative long-term follow-up lasted from 1 to 17 years (mean - 8.2±2.1 years). Results. An epileptogenic zone within single hemisphere was indentified in 66 (72.2%) cases, while bilateral epileptiform activity was observed in 25 (27.5%) children. The most common etiologies of epilepsy included hypoxic-ischemic encephalopathy, intracerebral hemorrhage, meningoencephalitis, Rasmussen syndrome, cortical dysplasia, tumors.After surgery 51 (56%) patients became seizures free (Engel 1), 14 (15.4%) patients had rare auras or focal seizures (Engel 2). In 25 (27.5%) cases, seizure frequency reduction was less than 75% or did not change significantly. The most favorable outcomes were associated with resection procedures, resulting in complete seizure control in 46 (69.7%) out of 66 children, with significant improvement observed in 9 (13.6%) cases. After callosotomy drop-attacks stopped in 14 (78%) out of 18 who had them before surgery. Operative complications were encountered in 6 (6.6%) cases, postoperative mortality occurred in 1 (1.1%) case. Conclusions. The key to the effectiveness of surgical treatment of childhood epilepsy is early surgical intervention, which leads to the control of epileptic seizures, correction of psychological and cognitive emotional disorders and improvement of quality of life. The combination of resection procedures and disconnections contributes to the reduction of epileptogenic neurons and suppression of epileptic discharges.

Estimation of fMRI responses related to epileptic discharges using Bayesian hierarchical modeling.

Simultaneous electroencephalography-functional MRI (EEG-fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null-hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty-two epilepsy patients who underwent EEG-fMRI and subsequent surgery were included in this study. A conventional voxel-wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel-wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long-lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel-wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG-fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.

Effects of Sodium Lactate Infusion in Two Girls with Glucose Transporter 1 Deficiency Syndrome.

Glucose is an important fuel for the brain. In glucose transporter 1 deficiency syndrome (GLUT1DS), the transport of glucose across the blood-brain barrier is limited. Most individuals with GLUT1DS present with developmental problems, epilepsy, and (paroxysmal) movement disorders, and respond favorably to the ketogenic diet. Similar to ketones, lactate is an alternative energy source for the brain. The aim of this study is to investigate whether intravenous infusion of sodium lactate in children with GLUT1DS has beneficial effects on their epilepsy. We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study. Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study. This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources.

The role of extracellular glutamate homeostasis dysregulated by astrocyte in epileptic discharges: a model evidence.

Glutamate (Glu) is a predominant excitatory neurotransmitter that acts on glutamate receptors to transfer signals in the central nervous system. Abnormally elevated extracellular glutamate levels is closely related to the generation and transition of epileptic seizures. However, there lacks of investigation regarding the role of extracellular glutamate homeostasis dysregulated by astrocyte in neuronal epileptic discharges. According to this, we propose a novel neuron-astrocyte computational model (NAG) by incorporating extracellular Glu concentration dynamics from three aspects of regulatory mechanisms: (1) the Gluuptake through astrocyte EAAT2; (2) the binding and release Glu via activating astrocyte mGluRs; and (3) the Glu free diffusion in the extracellular space. Then the proposed model NAG is analyzed theoretically and numerically to verify the effect of extracellular Glu homeostasis dysregulated by such three regulatory mechanisms on neuronal epileptic discharges. Our results demonstrate that the neuronal epileptic discharges can be aggravated by the downregulation expression of EAAT2, the aberrant activation of mGluRs, and the elevated Glu levels in extracellular micro-environment; as well as various discharge states (including bursting, mixed-mode spiking, and tonic firing) can be transited by their combination. Furthermore, we find that such factors can also alter the bifurcation threshold for the generation and transition of epileptic discharges. The results in this paper can be helpful for researchers to understand the astrocyte role in modulating extracellular Glu homeostasis, and provide theoretical basis for future related experimental studies.

CDKL5-mediated developmental tuning of neuronal excitability and concomitant regulation of transcriptome.

Cyclin-dependent kinase-like 5 (CDKL5) is a serine-threonine kinase enriched in the forebrain to regulate neuronal development and function. Patients with CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition caused by mutations of CDKL5 gene, present early-onset epilepsy as the most prominent feature. However, spontaneous seizures have not been reported in mouse models of CDD, raising vital questions on the human-mouse differences and the roles of CDKL5 in early postnatal brains. Here, we firstly measured electroencephalographic (EEG) activities via a wireless telemetry system coupled with video-recording in neonatal mice. We found that mice lacking CDKL5 exhibited spontaneous epileptic EEG discharges, accompanied with increased burst activities and ictal behaviors, specifically at postnatal day 12 (P12). Intriguingly, those epileptic spikes disappeared after P14. We next performed an unbiased transcriptome profiling in the dorsal hippocampus and motor cortex of Cdkl5 null mice at different developmental timepoints, uncovering a set of age-dependent and brain region-specific alterations of gene expression in parallel with the transient display of epileptic activities. Finally, we validated multiple differentially expressed genes (DEGs), such as glycine receptor subunit 2 and cholecystokinin, at the transcript and/or protein levels, supporting the relevance of these genes to CDKL5-regulated excitability. Our findings reveal early-onset neuronal hyperexcitability in mouse model of CDD, providing new insights into CDD etiology and potential molecular targets to ameliorate intractable neonatal epilepsy.

Ecstatic or Mystical Experience through Epilepsy.

Ecstatic epilepsy is a rare form of focal epilepsy, so named because the seizures' first symptoms consist of an ecstatic/mystical experience, including feelings of increased self-awareness, mental clarity, and "unity with everything that exists," accompanied by a sense of bliss and physical well-being. In this perspective article, we first describe the phenomenology of ecstatic seizures, address their historical context, and describe the primary brain structure involved in the genesis of these peculiar epileptic seizures, the anterior insula. In the second part of the article, we move onto the possible neurocognitive underpinnings of ecstatic seizures. We first remind the reader of the insula's role in interoceptive processing and consciously experienced feelings, contextualized by the theory of predictive coding. This leads us to hypothesize that temporary disruptions to activity in the anterior insula could interrupt the generation of interoceptive prediction errors, and cause one to experience the absence of uncertainty, and thereby, a sense of bliss. The absence of interoceptive prediction errors would in fact mimic perfect prediction of the body's physiological state. This sudden clarity of bodily perception could explain the ecstatic quality of the experience, as the interoceptive system forms the basis for unified conscious experience. Our alternative hypothesis is that the anterior insula plays an overarching role in the processing of surprise and that the dysfunction caused by the epileptic discharge could interrupt any surprise exceeding expectations, resulting in a sense of complete control and oneness with the environment.

Delayed Deterioration of Electroencephalogram in Patients with Cardiac Arrest: A Cohort Study.

The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings. This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality. We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU. Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure.

Cognitive dysfunction in drug-naïve late-onset temporal lobe epilepsy

ObjectivesTo evaluate cognitive functions including memory in middle-aged and elderly patients with antiseizure drug-naïve late-onset temporal lobe epilepsy (TLE). MethodsWe performed assessments with the Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R) in 26 antiseizure drug-naïve patients with late-onset TLE, in comparison to 30 healthy subjects. We investigated the relationships between these cognitive function scores and clinical characteristics, seizure frequency, and frequency of interictal epileptic discharges (IEDs). ResultsPatients with epilepsy had a significantly lower score than healthy controls in the verbal intelligence quotient (IQ), the performance IQ, and full-scale IQ in intelligence testing. Patients showed significantly decrease in the verbal memory scores, visual memory scores, general memory scores, and delayed recall scores compared with those in the control subjects.Delayed recall scores were significantly negatively correlated with recent seizure frequency and the total IEDs count per minute, but not with age of onset or duration of illness. SignificancePatients with antiseizure drug-naïve late-onset TLE displayed cognitive deficits including the domains of memory by using standard clinical neuropsychological test.Patients with late-onset epilepsy need to be considered for cognitive dysfunction at the time of diagnosis of TLE because they may have their daily life and work affected not only by epileptic seizures but also by cognitive deficits. Appearance of seizures and EEG abnormalities may affect the memory function in patients with late-onset TLE.

GFBLS: Graph-regularized fuzzy broad learning system for detection of interictal epileptic discharges

Epilepsy as the most common neurological disorder globally has drawn more and more attention. However, it is time-consuming and labor-intensive for manual detection of interictal epileptic discharges (IEDs). Thus, there is an urgent need to develop an efficient and automated detection approach as a more accurate diagnostic alternative for epilepsy detection. Recently, fuzzy broad learning system (FBLS) has been recognized as an alternative to deep learning and utilized in various fields. Nevertheless, FBLS ignores the locally invariant property of data. To effectively address this issue and further improve the performance of FBLS, a novel graph-regularized fuzzy broad learning system (GFBLS) is first proposed based on graph regularization. Moreover, an automated GFBLS-based approach is proposed for IEDs detection from EEG recordings. In the proposed method, graph convolutional neural networks (GCN) is firstly utilized to extract features from line graphs with undirected connections, which are constructed by EEG recordings, then extracted features by GCN are fed into GFBLS for IEDs detection. The experimental results demonstrated that GFBLS can achieve accuracy of 92.20%, specificity of 90.90% and precision of 91.13% with the training time of only 31.6 s, which is superior or comparable performance compared with other state-of-the-art approaches.

The spectrum of electroencephalographic characteristics in children with autistic spectrum disorder at a tertiary care centre

There are high rates of epileptiform EEGs in children with ASD without a history of seizures or epilepsy. ASD is associated with a higher risk of epilepsy with prevalence ranging from 5%-46%. The study was conducted to detect the prevalence of EEG abnormalities in ASD patients and to evaluate the spectrum of EEG changes in epileptic and nonepileptic patients with their clinical features and severity of ASD. The study was conducted at the tertiary care centre. A total of 140 cases with ASD, who met DSM V criteria for autism were studied. All the cases were screened with history taking, physical, neurological, and neuropsychiatric evaluation. These children were subjected to psychological testing using the ISAA scoring system. All the studied cases were also subjected to EEG testing. The prevalence of EEG changes (epileptic and non-epileptic discharges) in our study was 45%, with EEG changes seen in 28.44% of cases of ASD without seizure. In ASD cases with seizure, the most common seizure type was generalized tonic-clonic convulsion (GTCS), on the contrary, most common EEG changes were focal epileptiform activity. Most of EEG had shown well-formed background, except for few which were slow for age. The most dominant background rhythm was theta intermixed with delta followed by theta and delta intermixed with alpha in those children with seizures. Whereas, in children without a history of seizure, the dominant rhythm was delta theta alpha and theta delta. This may be due the o large number of EEG recordings being sleep EEG. We will like to hypothesize that the predominant EEG changes in the frontal lobe may have some neuronal link in the pathogenesis of behavior pattern in ASD. We also propose that more detailed study with different types of EEG and with a larger sample size should be done in the future.

Tetrastigma hemsleyanum suppresses neuroinflammation in febrile seizures rats via regulating PKC-δ/caspase-1 signaling pathway

Ethnopharmacological relevanceTetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum, Sanyeqing) has been used in the prevention and treatment of repetitive Febrile seizures (FS) over the centuries in China. Aim of the studyT. hemsleyanum exerts wide pharmacological action, which has been widely used for treating various diseases, including infantile febrile seizure. However, the systematic study on this herb's material basis and the functional mechanism is lacking. This study intended to systematically elucidate the mechanism of T. hemsleyanum against febrile seizures. Materials and methodsThe efficacy of T. hemsleyanum was estimated by using a hot bath as a model of FS, the onset and duration of seizure, morphological structure changes of hippocampal neurons as well as magnetoencephalography were applied to evaluate the effects. Meanwhile, the bioactive components of T. hemsleyanum responsible for the therapeutic effect of T. hemsleyanum on FS were identified by UPLC-MS/MS. Then we systematically elucidated the mechanism of T. hemsleyanum based on metabonomics, transcriptomics, network pharmacological and experimental validation. ResultsIn a hyperthermia-induced FS model of rats, T. hemsleyanum significantly increased the seizure latency and decreased seizure duration, alleviating the abnormal delta and gamma band activity during epileptic discharge. Furthermore, ten chemical components of ethanol extracts from T. hemsleyanum were identified by UPLC-MS/MS, including quercetin, kaempferol, and procyanidin B1 and so on, which was consistent with the network pharmacology prediction. The serum metabolomics indicated that T. hemsleyanum mainly acts on inflammation regulation and neuroprotection by the glycerophospholipid metabolism pathway. Ninety-two potential targets of T. hemsleyanum on FS were identified by network pharmacology, and TNF, IL-6, and IL-1β were considered the pivotal targets. In the hippocampus transcriptomics, 17 KEGG pathways were identified after T. hemsleyanum treatment compared with the FS model group, among which 15 pathways overlapped with those identified by network pharmacology, and the PKC-δ/caspase-1 signaling pathway was a critical node. Finally, in vivo experiments also verified T. hemsleyanum inhibited the activation of microglia and resulted in a significant reduction in the level of PKCδ, NLRC4, caspase-1, IL-1β, IL-6 and TNF-α in hippocampus of FS rats. ConclusionsOur study suggested that the therapeutic effect of T. hemsleyanum on FS might be regulated by inhibiting the neuroinflammation, thus exerting an anticonvulsant effect in vivo, and the mechanism might be related to regulating the PKC-δ/caspase-1 signaling pathway.

GluK2 Is a Target for Gene Therapy in Drug-Resistant Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. Here, we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated interictal-like epileptiform discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. ANN NEUROL 2023;94:745-761.

A Rare Cause of Developmental Epileptic Encephalopathy: D-Bifunctional Protein Deficiency with a Novel Pathogenic Variant

Abstract Peroxisomal disorders are rare causes of severe neonatal encephalopathies. Here we report a two-month old infant with refractory neonatal seizures evaluated with first-step metabolic screening in the neonatal intensive care unit. The screening did not indicate the inborn error of metabolism. In a series of electroencephalography (EEG) studies, multifocal epileptic discharges and electroclinic seizures were observed, suggesting epileptic encephalopathy. The analysis of plasma very-long-chain fatty acids indicated a peroxisomal disorder. Then a next-generation DNA sequencing panel of epileptic encephalopathy provided a D-Bifunctional Protein Deficiency (D-BP) with a novel mutant gene. The epilepsy panels with next-generation DNA sequencing, after the primarily metabolic screening for the differential diagnosis of early infantile epileptic encephalopathy, provide guidance for a definitive diagnosis. Next-generation genetic studies are essential in identifying subtypes of peroxisomal disorders because they have similar very-long-chain fatty acid levels and dysmorphic findings.

Connectivity alteration in thalamic nuclei and default mode network-related area in memory processes in mesial temporal lobe epilepsy using magnetoencephalography

This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.

Therapeutic effect of tempo in Mozart’s “Sonata for two pianos” (K. 448) in patients with epilepsy: An electroencephalographic study

BackgroundMozart’s “Sonata for two pianos” (Köchel listing 448) has proven effective as music therapy for patients with epilepsy, but little is understood about the mechanism of which feature in it impacted therapeutic effect. This study explored whether tempo in that piece is important for its therapeutic effect. MethodsWe measured the effects of tempo in Mozart’s sonata on clinical and electroencephalographic parameters of 147 patients with epilepsy who listened to the music at slow, original, or accelerated speed. As a control, patients listened to Haydn’s Symphony no. 94 at original speed. ResultsListening to Mozart’s piece at original speed significantly reduced the number of interictal epileptic discharges. It decreased beta power in the frontal, parietal, and occipital regions, suggesting increased auditory attention and reduced visual attention. It also decreased functional connectivity among frontal, parietal, temporal, and occipital brain regions, also suggesting increased auditory attention and reduced visual attention. No such effects were observed after patients listened to the slow or fast version of Mozart’s piece, or to Haydn’s symphony at normal speed. ConclusionsThese results suggest that Mozart’s “Sonata for two pianos” may exert therapeutic effects by regulating attention when played at its original tempo, but not slower or faster. These findings may help guide the design and optimization of music therapy against epilepsy.

EEG phase synchronization during absence seizures.

Absence seizures-generalized rhythmic spike-and-wave discharges (SWDs) are the defining property of childhood (CAE) and juvenile (JAE) absence epilepsies. Such seizures are the most compelling examples of pathological neuronal hypersynchrony. All the absence detection algorithms proposed so far have been derived from the properties of individual SWDs. In this work, we investigate EEG phase synchronization in patients with CAE/JAE and healthy subjects to explore the possibility of using the wavelet phase synchronization index to detect seizures and quantify their disorganization (fragmentation). The overlap of the ictal and interictal probability density functions was high enough to preclude effective seizure detection based solely on changes in EEG synchronization. We used a machine learning classifier with the phase synchronization index (calculated for 1 s data segments with 0.5 s overlap) and the normalized amplitude as features to detect generalized SWDs. Using 19 channels (10-20 setup), we identified 99.2% of absences. However, the overlap of the segments classified as ictal with seizures was only 83%. The analysis showed that seizures were disorganized in approximately half of the 65 subjects. On average, generalized SWDs lasted about 80% of the duration of abnormal EEG activity. The disruption of the ictal rhythm can manifest itself as the disappearance of epileptic spikes (with high-amplitude delta waves persisting), transient cessation of epileptic discharges, or loss of global synchronization. The detector can analyze a real-time data stream. Its performance is good for a six-channel setup (Fp1, Fp2, F7, F8, O1, O2), which can be implemented as an unobtrusive EEG headband. False detections are rare for controls and young adults (0.03% and 0.02%, respectively). In patients, they are more frequent (0.5%), but in approximately 82% cases, classification errors are caused by short epileptiform discharges. Most importantly, the proposed detector can be applied to parts of EEG with abnormal EEG activity to quantitatively determine seizure fragmentation. This property is important because a previous study reported that the probability of disorganized discharges is eight times higher in JAE than in CAE. Future research must establish whether seizure properties (frequency, length, fragmentation, etc.) and clinical characteristics can help distinguish CAE and JAE.

The ferroptosis inducer RSL3 triggers interictal epileptiform activity in mice cortical neurons.

Epilepsy is a neurological disorder characterized by recurrent seizures, which result from excessive, synchronous discharges of neurons in different brain areas. In about 30% of cases, epileptic discharges, which vary in their etiology and symptomatology, are difficult to treat with conventional drugs. Ferroptosis is a newly defined iron-dependent programmed cell death, characterized by excessive accumulation of lipid peroxides and reactive oxygen species. Evidence has been provided that ferroptosis is involved in epilepsy, and in particular in those forms resistant to drugs. Here, whole cell patch clamp recordings, in current and voltage clamp configurations, were performed from layer IV principal neurons in cortical slices obtained from adult mouse brain. Application of the ferroptosis inducer RAS-selective lethal 3 (RSL3) induced interictal epileptiform discharges which started at RSL3 concentrations of 2 μM and reached a plateau at 10 μM. This effect was not due to changes in active or passive membrane properties of the cells, but relied on alterations in synaptic transmission. In particular, interictal discharges were dependent on the excessive excitatory drive to layer IV principal cells, as suggested by the increase in frequency and amplitude of spontaneously occurring excitatory glutamatergic currents, possibly dependent on the reduction of inhibitory GABAergic ones. This led to an excitatory/inhibitory unbalance in cortical circuits. Interictal bursts could be prevented or reduced in frequency by the lipophilic antioxidant Vitamin E (30 μM). This study allows identifying new targets of ferroptosis-mediated epileptic discharges opening new avenues for the treatment of drug-resistant forms of epilepsy.

Structure-function coupling increases during interictal spikes in temporal lobe epilepsy: A graph signal processing study

ObjectiveStructure-function coupling remains largely unknown in brain disorders. We studied this coupling during interictal epileptic discharges (IEDs), using graph signal processing in temporal lobe epilepsy (TLE). MethodsWe decomposed IEDs of 17 patients on spatial maps, i.e. network harmonics, extracted from a structural connectome. Harmonics were split in smooth maps (long-range interactions reflecting integration) and coarse maps (short-range interactions reflecting segregation) and were used to reconstruct the part of the signal coupled (Xc) and decoupled (Xd) from the structure, respectively. We analysed how Xc and Xd embed the IED energy over time, at global and regional level. ResultsFor Xc, the energy was smaller than for Xd before the IED onset (p < .001), but became larger around the first IED peak (p < .05, cluster 2, C2). Locally, the ipsilateral mesial regions were significantly coupled to the structure over the whole epoch. The ipsilateral hippocampus increased its coupling during C2 (p < .01). ConclusionsAt whole-brain level, segregation gives way to integrative processes during the IED. Locally, brain regions commonly involved in the TLE epileptogenic network increase their reliance on long-range couplings during IED (C2). SignificanceIn TLE, integration mechanisms prevail during the IED and are localized in the ipsilateral mesial temporal regions.

Self-limited childhood epilepsies are disorders of the perisylvian communication system, carrying the risk of progress to epileptic encephalopathies-Critical review.

"Sleep plasticity is a double-edged sword: a powerful machinery of neural build-up, with a risk to epileptic derailment." We aimed to review the types of self-limited focal epilepsies..."i.e. keep as two separate paragraphs" We aimed to review the types of self-limited focal epilepsies: (1) self-limited focal childhood epilepsy with centrotemporal spikes, (2) atypical Rolandic epilepsy, and (3) electrical status epilepticus in sleep with mental consequences, including Landau-Kleffner-type acquired aphasia, showing their spectral relationship and discussing the debated topics. Our endeavor is to support the system epilepsy concept in this group of epilepsies, using them as models for epileptogenesis in general. The spectral continuity of the involved conditions is evidenced by several features: language impairment, the overarching presence of centrotemporal spikes and ripples (with changing electromorphology across the spectrum), the essential timely and spatial independence of interictal epileptic discharges from seizures, NREM sleep relatedness, and the existence of the intermediate-severity "atypical" forms. These epilepsies might be the consequences of a genetically determined transitory developmental failure, reflected by widespread neuropsychological symptoms originating from the perisylvian network that have distinct time and space relations from secondary epilepsy itself. The involved epilepsies carry the risk of progression to severe, potentially irreversible encephalopathic forms.