Spike Discharges Research Articles

Can occurrence of convulsive status epilepticus during video telemetry be predicted? Observations from an epilepsy monitoring unit

PurposeThe objective of the study was to evaluate the frequency, clinical, and video-electroencephalographic (VEEG) predictors of convlusive status epilepticus (CSE) in the epilepsy-monitoring unit (EMU). MethodsThe data of all patients who had CSE in our EMU between 2008 and 2017 were reviewed. For each case, two age- and diagnosis-matched subjects who underwent VEEG and did not develop CSE were taken as internal controls. Electro-clinical data of both the groups were compared. Predictors of CSE were assessed using logistic regression analysis. ResultsOut of 11,188 video-telemetries were conducted between 2008-17, forty-three events of CSE (0.38%) were recorded. On comparisons with 86 internal controls no differences were apparent on prevalence of cognitive impairment, structural lesion, number of baseline anti-seizure medications (ASM), ASM taper schedule, ictal patterns, and duration of VEEG monitoring. Inter-ictal rhythmic periodic patterns had significantly higher prevalence in cases (p = 0.028). Logistic regression analysis revealed that odds of CSE were higher with past history of SE [p = 0.008; adjusted odds ratio (OR) = 5.48 (confidence intervals {CI} 1.55–19.28)] and in presence of rhythmic spike and wave discharges [p = 0.016, OR = 33.518(CI = 1.93–581.4)]; the odds were lower if the first two seizures recorded did not evolve into CSE [p = 0.009, OR = 0.247 (CI = 0.08–0.70)] and if there was prior history of daily seizures [p = 0.02, OR = 0.250 (CI = 0.07–0.84)]. ConclusionCSE is a rare yet important adverse event in EMU. Clinical predictors are more relevant in comparison to EEG variables. Extent of ASM withdrawal may not directly account for occurrence of CSE; factors inherent to a patient’s epilepsy are deterministic.

Fly seizure EEG: field potential activity in the Drosophila brain

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the ‘bang-sensitive’ sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABAA blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants.

Spike and wave discharges and fast ripples during posttraumatic epileptogenesis.

The goal of the present study was to determine whether spike and wave discharges (SWDs) and SWDs with superimposed fast ripples (SWDFRs) could be biomarkers of posttraumatic epileptogenesis. Fluid percussion injury was conducted on 13-14-week old male Sprague Dawley rats. Immediately after traumatic brain injury (TBI), they were implanted with microelectrodes in the neocortex, hippocampus, and striatum bilaterally. Age-matched sham rats with the same electrode implantation montage acted as controls. Wideband brain electrical activity was recorded intermittently from Day 1 of TBI, and continued from 2 to 21weeks after TBI. SWD and SWDFR analysis was performed during the first 2 weeks to investigate whether the occurrence of this pattern predicted development of epilepsy. The remaining 3-21weeks were used for identifying which rats became epileptic (E+ group) and which did not (E- group). The E+ group (n=9) showed a significant increase in SWD rate in prefrontal cortex during Weeks 1 and 2 after TBI. The E- group showed a significant increase in SWD rate only in the second week. One hundred percent of rats in the E+ group displayed SWDFRs beginning from the first week after TBI. The SWDFR pattern was observed in all recorded brain areas: prefrontal and perilesional cortices, hippocampus, and striatum. None of rats in the E- group showed coexistence of fast ripples with SWDs. Occurrence of SWDFRs after TBI, but not an increase in the rate of SWDs, could be a noninvasive electroencephalographic biomarker of posttraumatic epileptogenesis.

From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research.

The electrographic hallmark of childhood absence epilepsy (CAE) and other idiopathic forms of epilepsy are 2.5–4 Hz spike and wave discharges (SWDs) originating from abnormal electrical oscillations of the cortico-thalamo-cortical network. SWDs are generally associated with sudden and brief non-convulsive epileptic events mostly generating impairment of consciousness and correlating with attention and learning as well as cognitive deficits. To date, SWDs are known to arise from locally restricted imbalances of excitation and inhibition in the deep layers of the primary somatosensory cortex. SWDs propagate to the mostly GABAergic nucleus reticularis thalami (NRT) and the somatosensory thalamic nuclei that project back to the cortex, leading to the typical generalized spike and wave oscillations. Given their shared anatomical basis, SWDs have been originally considered the pathological transition of 11–16 Hz bursts of neural oscillatory activity (the so-called sleep spindles) occurring during Non-Rapid Eye Movement (NREM) sleep, but more recent research revealed fundamental functional differences between sleep spindles and SWDs, suggesting the latter could be more closely related to the slow (<1 Hz) oscillations alternating active (Up) and silent (Down) cortical activity and concomitantly occurring during NREM. Indeed, several lines of evidence support the fact that SWDs impair sleep architecture as well as sleep/wake cycles and sleep pressure, which, in turn, affect seizure circadian frequency and distribution. Given the accumulating evidence on the role of astroglia in the field of epilepsy in the modulation of excitation and inhibition in the brain as well as on the development of aberrant synchronous network activity, we aim at pointing at putative contributions of astrocytes to the physiology of slow-wave sleep and to the pathology of SWDs. Particularly, we will address the astroglial functions known to be involved in the control of network excitability and synchronicity and so far mainly addressed in the context of convulsive seizures, namely (i) interstitial fluid homeostasis, (ii) K+ clearance and neurotransmitter uptake from the extracellular space and the synaptic cleft, (iii) gap junction mechanical and functional coupling as well as hemichannel function, (iv) gliotransmission, (v) astroglial Ca2+ signaling and downstream effectors, (vi) reactive astrogliosis and cytokine release.

Fast synaptic excitatory neurotransmission in the human submucosal plexus.

Acetylcholine is the main excitatory neurotransmitter in the enteric nervous system (ENS) in all animal models examined so far. However, data for the human ENS is scarce. We used neuroimaging using voltage and calcium dyes, Ussing chamber, and immunohistochemistry to study fast synaptic neurotransmission in submucosal plexus neurons of the human gut. Electrical stimulation of intraganglionic fiber tracts led to fast excitatory postsynaptic potentials (fEPSPs) in 29 submucosal neurons which were all blocked by the nicotinic antagonist hexamethonium. The nicotinic agonist DMPP mimicked the effects of electrical stimulation and had excitatory effects on 56 of 73 neurons. The unselective NMDA antagonist MK-801 blocked fEPSPs in 14 out of 22 neurons as well as nicotine evoked spike discharge. In contrast, the application of NMDA showed only weak effects on excitability or calcium transients. This agreed with the finding that the specific NMDA antagonist D-APV reduced fEPSPs in only 1 out of 40 neurons. Application of AMPA or kainite had no effect in 41 neurons or evoked spike discharge in only one out of 41 neurons, respectively. Immunohistochemistry showed that 98.7±2.4% of all submucosal neurons (n=6 preparations, 1003 neurons) stained positive for the nicotinic receptor (α1 , α2 or α3 -subunit). Hexamethonium (200µM) reduced nerve-evoked chloride secretion by 34.3±18.6% (n=14 patients), whereas D-APV had no effect. Acetylcholine is the most important mediator of fast excitatory postsynaptic transmission in human submucous plexus neurons whereas glutamatergic fEPSPs were rarely encountered.

Outcomes After Shortened Skilled Nursing Facility Stays Suggest Potential For Improving Postacute Care Efficiency.

Reducing postacute care in skilled nursing facilities (SNFs) in favor of home-based care is a leading cost-saving strategy in new payment models. Yet the extent to which SNF stays can be safely shortened remains unclear. We leveraged the exposure of fee-for-service Medicare beneficiaries without supplemental coverage to cost sharing after SNF benefit day 20 as a cause of shortened stays. Marked reductions in length-of-stay because of cost sharing shifted patients to home more than a week earlier than expected without cost sharing, producing a discharge spike. These reductions were not associated with clear evidence of compromised patient safety as measured by death, hospitalization for fall-related injuries, or all-cause hospitalization within nine days of the spike. Adverse consequences requiring hospitalization could not be excluded for a small proportion of shortened stays. These findings suggest potential for improving postacute care efficiency, as SNF stays may be unnecessarily long to ensure safety.

Kv3.1 channels regulate the rate of critical period plasticity

Experience-dependent plasticity within visual cortex is controlled by postnatal maturation of inhibitory circuits, which are both morphologically diverse and precisely connected. Gene-targeted disruption of the voltage-dependent potassium channel Kv3.1 broadens action potentials and reduces net inhibitory function of parvalbumin (PV)-positive GABA subtypes within the neocortex. In mice lacking Kv3.1, the rate of input loss from an eye deprived of vision was slowed two-fold, despite otherwise normal critical period timecourse and receptive field properties. Rapid ocular dominance plasticity was restored by local or systemic enhancement of GABAergic transmission with acute benzodiazepine infusion. Diazepam instead exacerbated a global suppression of slow-wave oscillations during sleep described previously in these mutant mice, which therefore did not account for the rescued plasticity. Rapid ocular dominance shifts closely reflected Kv3.1 gene dosage that prevented prolonged spike discharge of their target pyramidal cells in vivo or the spike amplitude decrement of fast-spiking cells during bouts of high-frequency firing in vitro. Late postnatal expression of this unique channel in fast-spiking interneurons thus subtly regulates the speed of critical period plasticity with implications for mental illnesses.

Positive allosteric modulation of type 1 cannabinoid receptors reduces spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg

Childhood Absence Epilepsy (CAE) accounts for approximately 10% of all pediatric epilepsies. Current treatments for CAE are ineffective in approximately 1/3 of patients and can be associated with severe side effects such as hepatotoxicity. Certain cannabinoids, such as cannabidiol (CBD), have shown promise in the treatment of pediatric epilepsies. However, CBD remains limited or prohibited in many jurisdictions, and has not been shown to have efficacy in CAE. Modulation of the type 1 cannabinoid receptor (CB1R) may provide more desirable pharmacological treatments. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of CAE, including cortical spike and wave discharges (SWDs). We have recently demonstrated that Δ9-tetrahydrocannabinol (THC) increases SWDs in GAERS whereas CBD decreases these events. Here, we characterized aspects of the endocannabinoid system in brain areas relevant to seizures in GAERS and tested whether positive allosteric modulators (PAMs) of CB1R reduced SWDs. Both female and male GAERS had reduced (>50%) expression of CB1R and elevated levels of the endocannabinoid 2-AG in cortex compared to non-epileptic controls (NEC). We then administered the CB1R PAMs GAT211 and GAT229 to GAERS implanted with cortical electrodes. Systemic administration of GAT211 to male GAERS reduced SWDs by 40%. Systemic GAT229 administration reduced SWDs in female and male GAERS. Intracerebral infusion of GAT229 into the cortex of male GAERS reduced SWDs by >60% in a CB1R-dependent manner that was blocked by SR141716A. Together, these experiments identify altered endocannabinoid tone in GAERS and suggest that CB1R PAMs should be explored for treatment of absence seizures.

How Can an Na+ Channel Inhibitor Ameliorate Seizures in Lennox-Gastaut Syndrome?

Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na+ channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na+ channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASDs) according to simplistic categorical grouping. The effect of rufinamide on the Na+ channel, cellular discharges, and seizure behaviors was quantitatively characterized in native neurons and mammalian models of epilepsy, and compared with the other Na+ channel inhibitors. With a much faster binding rate to the inactivated Na+ channel than phenytoin, rufinamide is distinctively effective if the seizure discharges chiefly involve short bursts interspersed with hyperpolarized interburst intervals, exemplified by spike and wave discharges (SWDs) on electroencephalograms. Consistently, rufinamide, but not phenytoin, suppresses SWD-associated seizures in pentylenetetrazol or AY-9944 models, which recapitulate the major electrophysiological and behavioral manifestations in typical and atypical absence seizures, including LGS. Na+ channel inhibitors shall have sufficiently fast binding to exert an action during the short bursts and then suppress SWDs, in which cases rufinamide is superior. For the epileptiform discharges where the interburst intervals are not so hyperpolarized, phenytoin could be better because of the higher affinity. Na+ channel inhibitors with different binding kinetics and affinity to the inactivated channels may have different antiseizure scope. A rational choice of ASDs according to in-depth molecular pharmacology and the attributes of ictal discharges is advisable. ANN NEUROL 2021;89:1099-1113.

GIS vibration test method and characteristic signal recognition

Based on the characteristics of GIS insulation and mechanical fault types and practical measurement experience, two typical vibration measurement methods, direct measurement method and natural frequency measurement method, are proposed in this paper. Then, based on the real data of experiment and field measurement, the vibration signals of typical insulation fault and mechanical fault such as spike discharge and end cover looseness are compared, analyzed and summarized, and their respective data characteristics are extracted, which can provide the basis for the determination of GIS vibration fault types.

Factors associated with neurodevelopment in preterm infants with systematic inflammation

BackgroundSeveral studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.MethodsThis prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.ResultsThe I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.ConclusionsSystemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.

The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study

The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits.

Active probing to highlight approaching transitions to ictal states in coupled neural mass models.

The extraction of electrophysiological features that reliably forecast the occurrence of seizures is one of the most challenging goals in epilepsy research. Among possible approaches to tackle this problem is the use of active probing paradigms in which responses to stimuli are used to detect underlying system changes leading up to seizures. This work evaluates the theoretical and mechanistic underpinnings of this strategy using two coupled populations of the well-studied Wendling neural mass model. Different model settings are evaluated, shifting parameters (excitability, slow inhibition, or inter-population coupling gains) from normal towards ictal states while probing stimuli are applied every 2 seconds to the input of either one or both populations. The correlation between the extracted features and the ictogenic parameter shifting indicates if the impending transition to the ictal state may be identified in advance. Results show that not only can the response to the probing stimuli forecast seizures but this is true regardless of the altered ictogenic parameter. That is, similar feature changes are highlighted by probing stimuli responses in advance of the seizure including: increased response variance and lag-1 autocorrelation, decreased skewness, and increased mutual information between the outputs of both model subsets. These changes were mostly restricted to the stimulated population, showing a local effect of this perturbational approach. The transition latencies from normal activity to sustained discharges of spikes were not affected, suggesting that stimuli had no pro-ictal effects. However, stimuli were found to elicit interictal-like spikes just before the transition to the ictal state. Furthermore, the observed feature changes highlighted by probing the neuronal populations may reflect the phenomenon of critical slowing down, where increased recovery times from perturbations may signal the loss of a systems' resilience and are common hallmarks of an impending critical transition. These results provide more evidence that active probing approaches highlight information about underlying system changes involved in ictogenesis and may be able to play a role in assisting seizure forecasting methods which can be incorporated into early-warning systems that ultimately enable closing the loop for targeted seizure-controlling interventions.

Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike-and-wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant-based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2hr. Injected THC (1-10mg/kg, i.p.) dose-dependently increased SWDs to over 200% of baseline. In contrast, CBD (30-100mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high-THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low-THC/high-CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pre-treatment with a CB1R antagonist (SR141716A) did not prevent the high-THC cannabis smoke from increasing SWDs, suggesting that the THC-mediated increase may not be CB1R-dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti-epileptic effect. Together these experiments provide initial evidence that acute phytocannabinoid administration exerts the biphasic modulation of SWDs and may differentially impact patients with AE.

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies.

Lennox-Gastaut syndrome (LGS), a childhood-onset severe developmental and epileptic encephalopathy (DEE), is an entity that encompasses a heterogenous group of aetiologies, with no single genetic cause. It is characterised by multiple seizure types, an abnormal EEG with generalised slow spike and wave discharges and cognitive impairment, associated with high morbidity and profound effects on the quality of life of patients and their families. Drug-refractory seizures are a hallmark and treatment is further complicated by its multiple morbidities, which evolve over the patient’s lifetime. This review provides a comprehensive overview of the current and future options for the treatment of seizures associated with LGS. Six treatments are specifically indicated as adjunct therapies for the treatment of seizures associated with LGS in the US: lamotrigine, clobazam, rufinamide, topiramate, felbamate and most recently cannabidiol. These therapies have demonstrated reductions in drop seizures in 15%–68% of patients across trials, with responder rates (≥ 50% reduction in drop seizures) of 37%–78%. Valproate is still the preferred first-line treatment, generally in combination with lamotrigine or clobazam. Other treatments frequently used off-label include the broad spectrum anti-epileptic drugs (AED) levetiracetam, zonisamide and perampanel, while recent evidence from observational studies has indicated that a newer AED, the levetiracetam analogue brivaracetam, may be effective and well tolerated in LGS patients. Other treatments in clinical development include fenfluramine in late phase III, perampanel, soticlestat–OV953/TAK-953, carisbamate and ganaxolone. Non-pharmacologic interventions include the ketogenic diet, vagus nerve stimulation and surgical interventions; these are also expanding, with the potential for less invasive techniques for corpus callosotomy that have promise for reducing complications. However, despite these advancements, patients continue to experience a significant burden. Because LGS is not a single entity, tailoring of treatment is needed as opposed to a ‘one size fits all’ approach. Further research is needed into the underlying aetiologies and pathophysiology of LGS, together with advancements in treatments that encompass the spectrum of seizures associated with this complex syndrome.

Control and analysis of epilepsy waveforms in a disinhibition model of cortex network

Considering the disinhibition circuit between inhibitory neuronal populations with different time scales in cortical neural networks, here we propose a novel model to describe the occurrences and transitions of epilepsy waveforms. With the model we can successfully simulate poly-spike complexes, which are common in electrophysiological experiments and focal epilepsy patients. Meanwhile, we focus on the dynamic transitions between epilepsy waveforms and normal state and are devoted to exploring effective electrical stimulation strategies. Results show that disinhibition can induce an epileptic bidirectional transition, which is from spike and wave discharges, to poly-spike complexes and then to low-voltage rapid discharge activity, or it is reversed. And fascinating dynamical transition behaviors can be induced by varying average inhibitory synaptic gain. Interestingly, after applying two different control signals (deep brain stimulation and oscillatory input) to the system, all epilepsy waveforms can be suppressed or even eliminated. Results shed light on the pathophysiological mechanisms of epilepsy and guide clinical treatment from a theoretical viewpoint.

Fisetin 8-C-glucoside as entry inhibitor in SARS CoV-2 infection: molecular modelling study

Coronaviruses are RNA viruses that infect varied species including humans. TMPRSS2 is gateway for SARS CoV-2 entry into the host cell. It causes proteolytic activation of spike protein and discharge of the peptide into host cell. The TMPRSS2 inhibition could be one of the approaches to stop the viral entry, therefore, interaction pattern and binding energies for Fisetin and TMPRSS2 have been explored in the present study. TMPRSS2 peptide was used for homology modelling and then for further study. Molecular docking score and MMGBSA Binding energy of Fisetin was better than Nafamostat, a known inhibitor of TMPRSS2. Post docking MM-GBSA free energy for Fisetin and Nafamostat was −42.78 and −21.11 kcal/mol, respectively. Fisetin forms H bond with Val 25, His 41, Lys 42, Lys 45, Glu 44, Ser186. Nafamostat formed H bonds with Lys 85, Asp 90, Asp 203. RMSD plots of TMPRSS2, TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex showed stable profile with very small fluctuation during entire simulation of 150 ns. Significant decrease in TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex fluctuation occurred around His 41, Glu 44, Gly 136, Ser 186 in RMSF study. During simulation Fisetin interaction was observed with residues Val 25, His 41, Glu 44, Lys 45, Lys 87, Gly 136, Gln 183, Ser 186 likewise interaction of Nafamostat with Lys 85, Asp 90, Asn 163, Asp 203 and Ser 205. Post simulation MM-GBSA free energy was found to be −51.87 ± 4.3 and −48.23 ± 4.39 kcal/mol for TMPRSS2 with Fisetin and Nafamostat, respectively. Communicated by Ramaswamy H. Sarma

Insights on the role of external globus pallidus in controlling absence seizures

Absence epilepsy, characterized by transient loss of awareness and bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) on electroencephalography (EEG) during absence seizures, is generally believed to arise from abnormal interactions between the cerebral cortex (Ctx) and thalamus. Recent animal electrophysiological studies suggested that changing the neural activation level of the external globus pallidus (GPe) neurons can remarkably modify firing rates of the thalamic reticular nucleus (TRN) neurons through the GABAergic GPe–TRN pathway. However, the existing experimental evidence does not provide a clear answer as to whether the GPe–TRN pathway contributes to regulating absence seizures. Here, using a biophysically based mean-field model of the GPe-corticothalamic (GCT) network, we found that both directly decreasing the strength of the GPe–TRN pathway and inactivating GPe neurons can effectively suppress absence seizures. Also, the pallido-cortical pathway and the recurrent connection of GPe neurons facilitate the regulation of absence seizures through the GPe–TRN pathway. Specifically, in the controllable situation, enhancing the coupling strength of either of the two pathways can successfully terminate absence seizures. Moreover, the competition between the GPe–TRN and pallido-cortical pathways may lead to the GPe bidirectionally controlling absence seizures, and this bidirectional control manner can be significantly modulated by the Ctx–TRN pathway. Importantly, when the strength of the Ctx–TRN pathway is relatively strong, the bidirectional control of absence seizures by changing GPe neural activities can be observed at both weak and strong strengths of the pallido-cortical pathway.These findings suggest that the GPe–TRN pathway may have crucial functional roles in regulating absence seizures, which may provide a testable hypothesis for further experimental studies and new perspectives on the treatment of absence epilepsy.

LGG-02. A BRAIN TUMOR DIAGNOSED AFTER TRANSITION TO THE DEPARTMENT OF ADULT NEUROSURGERY FROM THE DEPARTMENT OF PEDIATRICS

The patient was a 17-year-old boy with a history of 4 non-febrile convulsions at 15 and 16 years of age. He visited the Department of Pediatrics at a pediatric hospital. An electroencephalogram showed right frontal spike discharge. MRI was performed and judged to show no abnormality. The pediatric doctor diagnosed him with epilepsy. At 17 years old, he was referred to our Department of Adult Neurosurgery for transition. Physical and neurological examinations showed no abnormalities. Brain MRI showed right frontal cortical small tumor, with T1 low, T2 high, diffusion-weighted imaging low, and partial contrast enhancement. We diagnosed him with a brain tumor and symptomatic epilepsy. We surgically removed a right frontal cortical tumor. A pathological examination finalized the diagnosis of dysembryoplastic neuroepithelial tumor. MRI confirmed the total removal of the tumor. Anticonvulsant was started before surgery. No epileptic seizure was observed, so the anticonvulsant medication was gradually tapered and stopped at two years after the surgery. No epilepsy nor recurrence has been observed thus far. The problem with the initial management of this case at the Department of Pediatrics in the pediatric hospital was that the brain tumor was missed despite an MRI examination. Had the transition not happened, this brain tumor might not have been diagnosed. A brain tumor is a rare disease, and epilepsy is a common disease. However, in cases of non-febrile convulsion, a brain tumor should be considered. Collaboration within a single department, hospital and local area should be established.

Ganglion Cells with Sustained Activity in the Fish Retina and Their Possible Function in Evaluation of Visual Scenes

Background extracellular spike activity of single ganglion cells was recorded from axon terminals in the optic tectum of living immobilized fish. The sizes of the receptive fields of ON and OFF units with sustained responses (USR) amounted to 4–5° and were comparable with those of feature detectors. Generation of spike discharges by USR required contrast between the center and periphery of the receptive field. When there was no contrast, no spike activity appeared. The magnitude of the reaction was monotonically dependent on the level of this contrast. USR of both the ON and OFF types were connected with three types of cone (L, M, S). Both the center and periphery of the receptive field displayed color opponency, the center and periphery of the receptive field being opponent in terms of this characteristic. In other words, USR were double opponent and may thus take part in color discrimination. The simultaneous operation of feature detectors and ganglion cells with baseline activity separated into ON and OFF channels is represented retinotopically and may provide tectum opticum neurons with the visual scene information required for their function of controlling external attention.