Synchronous Discharges Research Articles

Mecamylamine inhibits seizure-like activity in CA1-CA3 hippocampus through antagonism to nicotinic receptors.

Cholinergic modulation of hippocampal network function is implicated in multiple behavioral and cognitive states. Activation of nicotinic and muscarinic acetylcholine receptors affects neuronal excitability, synaptic transmission and rhythmic oscillations in the hippocampus. In this work, we studied the ability of the cholinergic system to sustain hippocampal epileptiform activity independently from glutamate and GABA transmission. Simultaneous CA3 and CA1 field potential recordings were obtained during the perfusion of hippocampal slices with the aCSF containing AMPA, NMDA and GABA receptor antagonists. Under these conditions, spontaneous epileptiform discharges synchronous between CA3 and CA1 were recorded. Epileptiform discharges were blocked by addition of the calcium-channel blocker Cd2+ and disappeared in CA1 after a surgical cut between CA3 and CA1. Cholinergic antagonist mecamylamine abolished CA3-CA1 synchronous epileptiform discharges, while antagonists of α7 and α4β2 nAChRs, MLA and DhβE, had no effect. Our results suggest that activation of nicotinic acetylcholine receptors can sustain CA3-CA1 synchronous epileptiform activity independently from AMPA, NMDA and GABA transmission. In addition, mecamylamine, but not α7 and α4β2 nAChRs antagonists, reduced bicuculline-induced seizure-like activity. The ability of mecamylamine to decrease hippocampal network synchronization might be associated with its therapeutic effects in a wide variety of CNS disorders including addiction, depression and anxiety.

Pattern transition of neuronal networks induced by chemical autapses with random distribution

Abstract The difference of congenital inheritance and acquired development makes the autaptic distribution in different brain regions variant. To investigate the physiological regulation of autaptic structures on the nervous system, the effects of chemical autapses with random distribution on the dynamics of Newman-Watts small-world neuronal networks are systematically analyzed with the help of three network metrics. The autaptic occurring probability is first introduced to characterize the random distribution of autaptic structures. Numerical results show that the random distribution of chemical autapses can markedly modulate the electrophysiological activities of neuronal networks owing to the self-feedback function of excitatory autapses, not only promoting the transmission of neural signals, but also inducing the network-level stochastic resonance and the transition of network dynamics. Particularly, the autaptic random distribution can make subthreshold or chaotic neuronal networks generate the phase synchronization phenomena and eventually evolve into the synchronous periodic discharge state, which provides a strategy to achieve the complete synchronization through pattern transition. This study reveals the ability of the stochastic characteristics of autaptic structures to alter the evolution of network spatiotemporal patterns, which could contribute to the application of autaptic structures in physiological experiments or artificial neural networks.

Assessment of Oral Health Status in Epileptic Children and Healthy Children in Bengaluru City: A Comparative Study.

IntroductionEpilepsy is a neurological disorder, which is identified by repeated episodes of abnormal synchronous discharge of brain, resulting in several types of deficits. A percentage of them also have mental and motor deficits. Both the epileptic conditions and their medical management can influence oral health.ObjectiveTo assess and to compare the oral health status of epileptic children and the healthy children in Bengaluru city.Material and methodologyData was collected from the study group, which included 100 children between age-group 5 and 16 years registered under the Department of Neurology, Indira Gandhi Institute of Child Health (IGICH). Data collected from healthy children as control group and they visited Department of Pedodontics and Preventive Dentistry, VS Dental College & Hospital (VSDCH) for routine dental check-up. All subjects were examined by single qualified examiner. Gingival Index, plaque index, decayed missing filled teeth for primary teeth (dmft) and for permanent teeth (DMFT) were recorded for both study and control group. Other findings were also recorded such as injury to dentition or oral soft tissues and gingival hyperplasia as side effect of antiepileptic drug therapy.ResultsThere was no statistically significant difference found in dmft and DMFT between control group and study group. But, there was significant difference present in dmft and DMFT on gender basis between control and study group.ConclusionThe group of children with epilepsy suffer from several oral health problems such as dental caries, gingival enlargement, periodontal disease, and injuries of the oral cavity, which are associated with seizure-related trauma.How to cite this articleTiwari S, Verma RK, Dhull KS, et al. Assessment of Oral Health Status in Epileptic Children and Healthy Children in Bengaluru City: A Comparative Study. Int J Clin Pediatr Dent 2021;14(6):768–773.

Action potential subpopulations within human muscle sympathetic nerve activity: Discharge properties and governing mechanisms.

Sympathetic emissions directed towards the skeletal muscle circulation - muscle sympathetic nerve activity (MSNA) - represent a key mechanism for maintaining homeostasis and supporting human survival during physiological stress. Pulse-rhythmic bursts formed by the synchronous discharge of differently-sized sympathetic action potentials (APs) represent the primary characteristic of MSNA. Of the APs firing under baseline conditions (reflecting low-threshold c-fibre activity), a range of subpopulations exists, of which three general categories can be discussed based on their peak-to-peak amplitude in the filtered raw neurogram - small, medium, and large. These subpopulations express nonuniform discharge, recruitment, and synchronization patterns. The subpopulation of medium APs fires synchronously in most bursts, while the subpopulations of small and large APs fire less often. However, 30% of total AP discharge occurs asynchronously between sympathetic bursts, a pattern expressed most often by small APs. In response to physiological stress (e.g., baroreflex unloading), the subpopulation of medium APs exhibits the largest increase in firing probability and a subpopulation of previously-silent larger and faster-conducting APs (reflecting high-threshold c-fibre activity) becomes recruited. Heterogeneous discharge, synchronization, and recruitment thresholds among AP subpopulations stem from differential regulation within the sympathetic organization including the arterial baroreflex and paravertebral ganglia. Indeed, the arterial baroreflex strongly regulates medium APs at baseline and enhances its control over this subpopulation during periods of baroreflex unloading. Conversely, small and large APs express weak baroreflex control. Trimethaphan infusion has revealed that ganglionic processes including nicotinic and non-nicotinic mechanisms may contribute to heterogenous firing behaviours among low-threshold AP subpopulations. This review highlights recent work revealing new insight to the discharge properties expressed by, and mechanisms governing, AP subpopulations within human MSNA.

Iron Metabolism and Ferroptosis in Epilepsy.

Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

Comparison of spatial distribution of active substances and sterilization range generated by array of printed-circuit-board plasma jets

By copper deposited in the holes of two perforated printed circuit boards to form copper rings with a radius and width of 1.5 mm as electrodes, a 4 × 4 plasma-jet-array device equipped with ring-ring electrode structure can realize stable and synchronous discharge of each unit. On the other hand, the transposition of the active substances on the agar plate produced by atmospheric-pressure plasma-jet array was visualized using a KI-starch reagent. It showed that the shape of the distribution of active substances can change from a ring to a solid circle when the gas-flow rate was reduced below 8 slm. In particular, the inactivation range of Escherichia coli at 90 s and inactivation range of Staphylococcus aureus at 180 s using this device were both close to twice the array area when the gas-flow rate was 5 slm. • A two-dimensional 4 × 4 array atmospheric pressure plasma jet device was manufactured by using PCB technology. • The transposition of the active substances on the agar plate was visualized using a KI-starch reagent. • The distribution shape of active substances can change from ring to solid circle when the gas flow rate was reduced. • The spatial distribution of active substances and sterilization range are good fit.

Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs.

Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats.

Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.

Efficient Power Transfers in Piezoelectric Energy-Harvesting Switched-Inductor Chargers

Piezoelectric -harvesting transducers can draw power from motion that can be used to energize a host of wireless microsystems that sense, process, and share vital information across a network. Since these tiny devices draw little power, maximizing the power they transfer is critical. Synchronized-discharge circuits are popular in this space because they can collect all the charge from the transducer and increase drawn power. Pre-charging the transducer can draw even more power, but only as much as voltage-breakdown limits allow. This brief examines how synchronous discharge circuits can output the most power possible from tiny difficult-to-overdamp piezoelectric transducers. Measurements will show how pre-charge symmetry and energy-transfer schemes alter the power drawn from the transducer and the power lost in the system. The charges are tested with a 10×50×1-mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3 </sup> 15-nF transducer generates up to 10 μA at 100 Hz and the breakdown voltage of the harvester circuit is 3 V. Indirect and direct transfers with symmetric pre-charges output 21% and 43% more power with the same inductor than the 4.2 μW that indirect transfers without pre-charge can generate. Generating the highest power possible is important because, with more power, tiny piezoelectric transducers can power wireless microsensors with greater functionality and longer lifetime.

Sleep and Epilepsy Link by Plasticity.

We aimed to explore the link between NREM sleep and epilepsy. Based on human and experimental data we propose that a sleep-related epileptic transformation of normal neurological networks underlies epileptogenesis. Major childhood epilepsies as medial temporal lobe epilepsy (MTLE), absence epilepsy (AE) and human perisylvian network (PN) epilepsies - made us good models to study. These conditions come from an epileptic transformation of the affected functional systems. This approach allows a system-based taxonomy instead of the outworn generalized-focal classification. MTLE links to the memory-system, where epileptic transformation results in a switch of normal sharp wave-ripples to epileptic spikes and pathological high frequency oscillations, compromising sleep-related memory consolidation. Absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) belong to the corticothalamic system. The burst-firing mode of NREM sleep normally producing sleep-spindles turns to an epileptic working mode ejecting bilateral synchronous spike-waves. There seems to be a progressive transition from AE to JME. Shared absences and similar bilateral synchronous discharges show the belonging of the two conditions, while the continuous age windows - AE affecting schoolchildren, JME the adolescents - and the increased excitability in JME compared to AE supports the notion of progression. In perisylvian network epilepsies - idiopathic focal childhood epilepsies and electrical status epilepticus in sleep including Landau-Kleffner syndrome - centrotemporal spikes turn epileptic, with the potential to cause cognitive impairment. Postinjury epilepsies modeled by the isolated cortex model highlight the shared way of epileptogenesis suggesting the derailment of NREM sleep-related homeostatic plasticity as a common step. NREM sleep provides templates for plasticity derailing to epileptic variants under proper conditions. This sleep-origin explains epileptiform discharges' link and similarity with NREM sleep slow oscillations, spindles and ripples. Normal synaptic plasticity erroneously overgrowing homeostatic processes may derail toward an epileptic working-mode manifesting the involved system's features. The impact of NREM sleep is unclear in epileptogenesis occurring in adolescence and adulthood, when plasticity is lower. The epileptic process interferes with homeostatic synaptic plasticity and may cause cognitive impairment. Its type and degree depends on the affected network's function. We hypothesize a vicious circle between sleep end epilepsy. The epileptic derailment of normal plasticity interferes with sleep cognitive functions. Sleep and epilepsy interconnect by the pathology of plasticity.

State-dependent modulation of sympathetic firing by α1-adrenoceptors requires constitutive PKC activity in the neonatal rat spinal cord.

The central adrenergic and noradrenergic neurotransmitter systems diffusively affect the operation of the spinal neural network and dynamically gauge central sympathetic outflow. Using in vitro splanchnic nerve-thoracic spinal cord preparations as an experimental model, this study examined the intraspinal α1-adrenoceptor-meidated modulation of sympathetic firing behaviors. Several sympathetic single-fiber activities were simultaneously recorded. Application of phenylephrine (Phe, an α1-adrenoceptor agonist) increased, decreased or did not affect spontaneous firing. A log-log plot of the change ratios of the average firing rates (AFR) versus their basal AFR displays a linear data distribution. Thus, the heterogeneity in α1-adrenoceptor-mediated responses is well described by a power law function. Phe-induced power-law firing modulation (plFM) was sensitive to prazosin (Prz, an α1-adrenoceptor antagonist). Heparin (Hep, a competitive IP3 receptor blocker) and chelerythrine (Che, a protein kinase C inhibitor) also caused plFM. Phe-induced plFM persisted in the presence of Hep; however, it was occluded by Che pretreatment. Pair-wise analysis of single-fiber activities revealed synchronous sympathetic discharges. Application of Phe, Hep or Che suppressed synchronous discharges in fiber pairs with apparent correlated firing (ACF) and induced or potentiated synchronous discharges in those without or with minimal ACF. Thus, the basal activities of the sympathetic preganglionic neurons participate in determining the responses mediated by the activation of α1-adrenoceptors. This deterministic factor, which is intrinsic to spinal neural networks, helps the supraspinal adrenergic and noradrenergic systems differentially control their widely distributed neural targets.

Coupling mechanical and electrical nonlinearities: The effect of synchronized discharging on tristable energy harvesters

Vibrational energy harvesters, and more particularly piezoelectric devices, usually feature two limitations: their narrow frequency band and their relatively limited conversion abilities. The first issue is typically addressed using mechanical nonlinearities introducing a polynomial stiffness, while the second concern may be overcome through nonlinear electrical interfaces. However, combining these two approaches is not straightforward because of the backward coupling which can make the energy harvesting process enhancement affecting the nonlinear mechanical behavior. Hence, the purpose of this paper is to expose and deeply investigate, both theoretically and experimentally, an energy harvesting system coupling such mechanical and electrical nonlinearities. Such a multinonlinear device is achieved through the combination of tristability on the mechanical side and a technique of synchronous discharge on the electrical aspect. Analytical investigations together with experimental measurements therefore show that the energy extraction magnification brought by the electrical interface may compromise the bandwidth enhancement offered by the nonlinear stiffness due to the coupled multiphysic nature of the device that yields damping effect. Ways of controlling the trade-off between bandwidth and power conversion are also devised through the introduction of a phase delay in the electrical switch command.

Thermal performance of dual S-channel air-type phase change energy storage device

The air-type phase change energy storage device (AT–PCESD) exchanges heat with air and uses the latent heat from the phase change materials (PCMs). The dual S-channel AT–PCESD can store and release heat separately and shortens the length of the device. Both the numerical simulation method and experimental verification were used to analyze its thermal performance. The difference between an S-channel and a straight channel was compared, and multi-condition simulations were carried out to explore the effects of air temperature, flow rate, and thermal conductivity of the PCMs. Furthermore, the heat releasing cut-in time during simultaneous heat storage and discharge conditions on the thermal performance and heat storage capacity was also analyzed. Increasing the hot air temperature, flow rate, and thermal conductivity of the PCMs can help shorten the heat storage time (9.3–51.2%) with varying characteristics, and it has a great impact on the heat storage capacity, which is about 26,000 KJ. Increasing the flow rate can increase the heat storage and heat release rates, with 4 m/s being the best flow rate. When the storage temperature difference is greater than the heat discharge temperature difference, turning on the synchronous storage and discharge conditions can continue to increase the liquid phase rate.

Cognitive Impairments in Touchscreen-based Visual Discrimination and Reversal Learning in Genetic Absence Epilepsy Rats from Strasbourg

Absence Epilepsy (AE) is associated with recurrent losses of awareness and synchronous bilateral spike-wave discharges (SWDs). While seizures do not generally continue into adulthood, cognitive and behavioral comorbidities persist. One preclinical model used to investigate AE is the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) which consistently have bilateral SWDs and similar behavioral profiles. In this experiment, we characterized discrimination learning and behavioral flexibility in female and male GAERS (n = 7 per sex) and Non-Epileptic Controls (NEC; n = 8 per sex) in a touchscreen-based version of visual discrimination (VD) and reversal learning (RL). We found that, on average, female GAERS required more sessions (12.3) to complete pretraining compared to female and male NEC (8.2 and 7.3, respectively) and male GAERS (9.4). In contrast, there was a sex-specific impairment during VD with male GAERS requiring more sessions on average (12.3) than male and female NEC (both 7.5) and female GAERS (8.3). Additionally, male GAERS completed >30% more selection and correction trials during VD and made >30% more errors.Both female and male GAERS required more sessions on average (9.1 and 10.7, respectively) of RL compared to female and male NEC (6.4 and 6.0 sessions, respectively). Accordingly, GAERS performed ∼30% more selection trials and correction trials compared to NEC, although only male GAERS made significantly more errors (>40%). Deficits in VD and RL were not associated with differences in correct or incorrect response latency, or reward collection latency, suggesting impairments are not due to alterations in locomotor activity or motivation. Together, these data suggest that GAERS have impaired behavioral flexibility and identify some sex-dependent differences. Thus, GAERS may be suitable for assessing the potential benefit of antiepileptic drugs on comorbid behavioral and cognitive deficits.

Involvement of nNOS, and α1, α2, β1, and β2 Subunits of Soluble Guanylyl Cyclase Genes Expression in Anticonvulsant Effect of Sumatriptan on Pentylenetetrazole-Induced Seizure in Mice.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Sumatriptan is a selective agonist of 5-Hydroxytryptamine1B/D auto-receptor, has been reassessed for its neuroprotection. This study was aimed to explore the anticonvulsant effect of sumatriptan through possible involvement of NO-cGMP pathway in mice. For this purpose, the protective effect of sumatriptan on PTZ-induced clonic seizure threshold (CST) was measured using NO-cGMP pathway inhibitors including N(G)-nitro-L-arginine (L-NNA, 1, 5, and 10 mg/kg), 7-nitroindazole (7-NI, 30, 45, and 60 mg/kg), aminoguanidine (AG, 30, 50, and 100 mg/kg), methylene blue (MB, 0.1, 0.5, and 1 mg/kg) and sildenafil (5, 10, and 20 mg/kg). The involvement of nitrergic system was further confirmed by measurement of nitrite levels by Griess reaction. The gene expression of neuronal nitric oxide synthase (nNOS) and subunits of soluble guanylyl cyclase (sGC) was studied using qRT-PCR analysis. Acute administration of sumatriptan (1.2 and 0.3 mg/kg) in combination with subeffective doses of NOS, sGC, and phosphodiesterase 5 inhibitors significantly reversed the PTZ-induced CST (P ≤ 0.001). The nitrite level in prefrontal cortex was significantly attenuated by sumatriptan (P ≤ 0.01). Furthermore, sumatriptan downregulated the PTZ-induced mRNA expression of nNOS (P ≤ 0.01), α1 (P ≤ 0.001), α2 (P ≤ 0.05), and β1 (P ≤ 0.05) genes in cerebral cortex of mice. In conclusion, the anticonvulsant activity of sumatriptan at least, in part, is mediated through inhibiting NO-cGMP pathway.

A review on epileptic foci localization using resting-state functional magnetic resonance imaging.

Epilepsy is a brain syndrome caused by synchronous abnormal discharge of brain neurons. As an effective treatment for epilepsy, successful surgical resection requires accurate localization of epileptic foci to avoid iatrogenic disability. Previous studies have demonstrated the potential of restingstate functional magnetic resonance imaging (rs-fMRI) technique to localize epileptic foci though clinical applications of rs-fMRI are still at an early stage of development. fMRI data analysis approaches seek pre-defined regressors modeling contributions to the voxel time series, including the BOLD response following neuronal activation. In present study, localization strategies of epileptic foci in rs-fMRI technology were classified and summarized. To begin with, data-driven approaches attempting to determine the intrinsic structure of the data were discussed in detail. Then, as novel fMRI data analysis methods, deconvolution algorithms such as total activation (TA) and blind deconvolution were discussed, which were applied to explore the underlying activity-inducing signal of the BOLD signal. Lastly, effective connectivity approaches such as autocorrelation function method and Pearson correlation coefficient have also been proposed to identify the brain regions driving the generation of seizures within the epileptic network. In the future, fMRI technology can be used as a supplement of intraoperative subdural electrode method or combined with traditional epileptic focus localization technologies, which is one of the most attractive aspect in clinic. It may also play an important role in providing diagnostic information for epilepsy patients.

Subiculum as a Generator of Sharp Wave-Ripples in the Rodent Hippocampus

Sharp waves ripples (SWRs) represent synchronous discharges of hippocampal neurons and are believed to play a major role in memory consolidation. A large body of evidence suggests that SWRs are exclusively generated in the CA3-CA2 network. In contrast, here we provide several lines of evidence showing that the subiculum can function as a secondary SWRs generator. SWRs with subicular origin propagate forward into the entorhinal cortex as well as backward into the hippocampus proper. Our findings suggest that the output structures of the hippocampus are not only passively facilitating the transfer of SWRs to the cortex but they can actively contribute to SWRs genesis. We hypothesize that SWRs with subicular origin may be important for the consolidation of information conveyed to the hippocampus via the temporoammonic pathway.

Presence of synchrony-generating hubs in the human epileptic neocortex.

•Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. •In the present study, we show that epileptiform interictal-like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the spontaneously occurring synchronous population activity. •Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non-epileptic patients. •Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. •These results help us to understand the role of excitatory and inhibitory neurons in synchrony-generating mechanisms, in both epileptic and non-epileptic conditions. Understanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24-channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABAA receptors, and several variations of spatially and temporally simple or complex interictal-like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one-half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal-like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition-induced epileptiform events were initiated mainly by non-synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.

A hybrid Local Binary Pattern and wavelets based approach for EEG classification for diagnosing epilepsy

Epilepsy is one of the grave neurological ailments affecting approximately 70 million people globally. Detection of epileptic attack is commonly carried out by viewing and analysing long-duration multi-channel EEG records. To counter this time-consuming process, a hybrid Local Binary Pattern-Wavelet based approach, classifying EEG in epileptic patients, is adopted in this research. Epilepsy is characterized by multiple ictal patterns in the form of synchronous epileptiform discharge transients. This work attempts to classify seizure from normal EEG recordings using the low-frequency activity. In order to perform this classification, the EEG signal is filtered and then transformed using Local Binary Pattern (LBP) into a new signal. Discrete Wavelet Transform (DWT) is employed to decompose the obtained signal. Wavelet coefficients are calculated to 5 levels of decomposition. A combination of univariate and bivariate features forms the feature set for seizure detection. This feature set extracted from low-frequency band coefficients helps in bringing out the dispersion, symmetry, and peakedness present in the EEG signal. A novel LBP based Spatio-temporal analysis of the continuous EEG signal for epilepsy detection is carried out on 105 seizures from 14 randomly selected subjects of CHB-MIT EEG database. A sensitivity of 100% is achieved on the CHB-MIT database while long term EEG is being tested with Linear Discriminant Analysis (LDA) classifier. The algorithm works well to obtain a false detection rate (FP/Hour) of 0.59. The specificity of 99.8% is attained with a mean accuracy of 99.6% when tested on 498.9 h of EEG data.

IN SILICO DESIGN OF POTENTIAL 1, 5-BENZOTHIAZEPINE DERIVATIVES AS AN ANTI - CONVULSANT AGENT BY MOLECULAR DOCKING STUDIES

Epilepsy is characterized by the presence of recurrent seizures. A seizure can be defined as “an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex”. One in every three patients with epilepsy is probable to be severely disabled. It is continuing this scenario as an attempt to develop potent and nontoxic anti-convulsant agents. Recently the discovery of benzothiazepine derivatives as an anticonvulsant agent is a significant area for research in medicinal chemistry as it is free from all side effects which is shown by a developed as an anticonvulsant agent. In this paper, we have presented results of 2D, and 3D docking poses studies of a series of 300 (Three series) molecules containing 1,5-benzothiazepine pharmacophore as anti-convulsant agents. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. All the molecules exhibited a binding score in the range of -82.61 to - 118.25 kcal/mol. Most active molecules from Series 1, 2 and 3 exhibited hydrogen bond interactions with LEU282B, LEU282B and LEU282B. Also for the selected standard sodium phenytoin showed the hydrogen bond interaction with LYS637A. It was noted that the docking score of 1a to 10a, 101b to 110b and 201c to 210c was almost the same as that of selected standard sodium phenytoin. The protein showed hydrogen bonding with all synthesized compound showed potential against epilepsy with GABA nergic mechanism. &#x0D; Keywords: Anti-convulsant; 1,5-benzothiazepine; V-Life MDS 4.3.