Spike Onset Research Articles

Overlap of spike and ripple propagation onset predicts surgical outcome in epilepsy.

Interictal biomarkers are critical for identifying the epileptogenic focus. However, spikes and ripples lack specificity while fast ripples lack sensitivity. These biomarkers propagate from more epileptogenic onset to areas of spread. The pathophysiological mechanism of these propagations is elusive. Here, we examine zones where spikes and high frequency oscillations co-occur (SHFO), the spatiotemporal propagations of spikes, ripples, and fast ripples, and evaluate the spike-ripple onset overlap (SRO) as an epilepsy biomarker. We retrospectively analyzed intracranial EEG data from 41 patients with drug-resistant epilepsy. We mapped propagations of spikes, ripples, and fast ripples, and identified their onset and spread zones, as well as SHFO and SRO. We then estimated the SRO prognostic value in predicting surgical outcome and compared it to onset and spread zones of spike, ripple, and fast ripple propagations, and SHFO. We detected spikes and ripples in all patients and fast ripples in 12 patients (29%). We observed spike and ripple propagations in 40 (98%) patients. Spike and ripple onsets overlapped in 35 (85%) patients. In good outcome patients, SRO showed higher specificity and precision (p < 0.05) in predicting resection compared to onset and zones of spikes, ripples, and SHFO. Only SRO resection predicted outcome (p = 0.01) with positive and negative predictive values of 82% and 57%, respectively. SRO is a specific and precise biomarker of the epileptogenic zone whose removal predicts outcome. SRO is present in most patients with drug-resistant epilepsy. Such a biomarker may reduce prolonged intracranial monitoring and improve outcome.

Surgical Outcomes of a Human Umbilical Cord Allograft Over the Ahmed Glaucoma Valve Plate for Refractory Glaucoma.

To report the surgical outcomes of sterile dehydrated human umbilical cord allograft over the Ahmed glaucoma valve (AGV) plate for refractory glaucoma. Thirty-four eyes of 34 patients with refractory glaucoma who underwent AGV with umbilical cord allograft (AmnioPlast THICK™; Life Cell International Private Limited, Mumbai, India) placed over the AGV plate between September 2021 and 2022 at a tertiary eye care centre were included (group1) and compared with 30 eyes of 30 patients undergoing AGV without amnioblasts (group 2). The intraocular pressure (IOP) at day one, one month, six months, and final IOP; the necessity for medications; or additional surgeries for IOP control were extracted from the hospital database. Success was defined as achieving an IOP below 22 mm Hg with or without glaucoma medications. IOP spikes after surgery were identified as a rise in pressure beyond 22 mm Hg at any point beyond six weeks post-surgery following an initial reduction of pressure exceeding 30% from the baseline pre-surgical IOP. A notable reduction in intraocular pressure (37 ± 7.9 mm Hg preoperative versus 14 ± 3.7 mm Hg at the final follow-up and 28 ± 3.6 mm Hg versus 18 ± 6.7 mm Hg in group 1 and 2, respectively) was observed in all eyes, with successful outcomes observed in 23 out of 34 eyes (67%). Ten eyes experienced a pressure spike, occurring at a median time of 12 months (range: 6-18 months), predominantly beyond six months post-surgery in group 1, while group 2 had similar pressure spikes in 21 of 30 eyes at a median time of two months (range: 1-5 months). No eyes necessitated supplementary glaucoma procedures, concluding with a final IOP of 14 ± 3.7 mm Hg at 1.9 ± 0.8 years. Vision loss occurred in only one of the 11 eyes that failed owing to non-glaucoma-related causes in group 1. The human umbilical cord allograft plate over the AGV plate may help in postponing the onset of intraocular pressure spikes beyond traditionally defined timelines. This helps in reducing and delaying the hypertensive phase occurring due to fibrosis.

How neuronal morphology impacts the synchronisation state of neuronal networks.

The biophysical properties of neurons not only affect how information is processed within cells, they can also impact the dynamical states of the network. Specifically, the cellular dynamics of action-potential generation have shown relevance for setting the (de)synchronisation state of the network. The dynamics of tonically spiking neurons typically fall into one of three qualitatively distinct types that arise from distinct mathematical bifurcations of voltage dynamics at the onset of spiking. Accordingly, changes in ion channel composition or even external factors, like temperature, have been demonstrated to switch network behaviour via changes in the spike onset bifurcation and hence its associated dynamical type. A thus far less addressed modulator of neuronal dynamics is cellular morphology. Based on simplified and anatomically realistic mathematical neuron models, we show here that the extent of dendritic arborisation has an influence on the neuronal dynamical spiking type and therefore on the (de)synchronisation state of the network. Specifically, larger dendritic trees prime neuronal dynamics for in-phase-synchronised or splayed-out activity in weakly coupled networks, in contrast to cells with otherwise identical properties yet smaller dendrites. Our biophysical insights hold for generic multicompartmental classes of spiking neuron models (from ball-and-stick-type to anatomically reconstructed models) and establish a connection between neuronal morphology and the susceptibility of neural tissue to synchronisation in health and disease.

Chemo- and bio-stratigraphic constraints on Cretaceous-Paleocene biotic turnover in the southern Tethys low-oxygen margin, Egypt

The late Cretaceous-Danian (K-Pg) organic-rich sequence is a global archive that witnessed abrupt paleo-condition changes during a high sea-level. In Egypt, this sequence is present in the Duwi and Dakhla formations as an E-W belt from the Red Sea to the Western Desert. We analyzed elemental and isotopic distributions in an age-constrained core from the Quseir area to understand paleoclimatic and paleoenvironmental factors influencing its deposition. Calcareous nannofossil and the chemical index of alteration (CIA) confirm a global cooling trend during the late Cretaceous, with two warming episodes indicating early phases of the Deccan volcanism. The Danian stage experienced a warm climate and intense chemical weathering. Mo-U enrichment factors covariation suggest deposition under oxygen-deficient conditions with evident watermass restrictions. High-productivity-indicating taxa were more abundant in Danian strata than in late Cretaceous strata, consistent with organic carbon characteristics. The δ13COrg-δ15N data show temporal heterogeneity due to organic matter type, redox conditions, preservation, stratigraphic condensation, and recycling of isotopically-light CO2. The negative δ13COrg shift around the K-Pg transition is globally correlative. Dynamic pyrite δ34S distribution resulted from variation in riverine influx, degree of pore-water openness, sulfate reduction rate, and diagenetic disproportionation of sulfur intermediates. Generally, radiogenic 187Os/188Os values were observed that were seemingly influenced by continental weathering and subsequent runoff influx of 187Os/188Os under a greenhouse climate. A positive 187Os/188Os shift to 3.68 (187Os/188Osi of 0.74) occurred at the onset of the Dakhla organic-rich spike. However, without a precise correlative stratigraphic framework, a global or regional seawater isotopic shift cannot be confirmed. We suggest that temporal variations in organic matter composition, redox, watermass conditions, and isotope fractionation of the K-Pg sequence in the study area were driven by discrepancies in climate, sea-level, and tectonic uplift. Further integrated approaches are needed to explore the geospheric drivers of this organic-rich sequence in time-equivalent sections.

High frequency oscillations in relation to interictal spikes in predicting postsurgical seizure freedom

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation.

Spike propagation mapping reveals effective connectivity and predicts surgical outcome in epilepsy.

Neurosurgical intervention is the best available treatment for selected patients with drug resistant epilepsy. For these patients, surgical planning requires biomarkers that delineate the epileptogenic zone, the brain area that is indispensable for the generation of seizures. Interictal spikes recorded with electrophysiological techniques are considered key biomarkers of epilepsy. Yet, they lack specificity, mostly because they propagate across brain areas forming networks. Understanding the relationship between interictal spike propagation and functional connections among the involved brain areas may help develop novel biomarkers that can delineate the epileptogenic zone with high precision. Here, we reveal the relationship between spike propagation and effective connectivity among onset and areas of spread and assess the prognostic value of resecting these areas. We analysed intracranial EEG data from 43 children with drug resistant epilepsy who underwent invasive monitoring for neurosurgical planning. Using electric source imaging, we mapped spike propagation in the source domain and identified three zones: onset, early-spread and late-spread. For each zone, we calculated the overlap and distance from surgical resection. We then estimated a virtual sensor for each zone and the direction of information flow among them via Granger causality. Finally, we compared the prognostic value of resecting these zones, the clinically-defined seizure onset zone and the spike onset on intracranial EEG channels by estimating their overlap with resection. We observed a spike propagation in source space for 37 patients with a median duration of 95 ms (interquartile range: 34-206), a spatial displacement of 14 cm (7.5-22 cm) and a velocity of 0.5 m/s (0.3-0.8 m/s). In patients with good surgical outcome (25 patients, Engel I), the onset had higher overlap with resection [96% (40-100%)] than early-spread [86% (34-100%), P = 0.01] and late-spread [59% (12-100%), P = 0.002], and it was also closer to resection than late-spread [5 mm versus 9 mm, P = 0.007]. We found an information flow from onset to early-spread in 66% of patients with good outcomes, and from early-spread to onset in 50% of patients with poor outcome. Finally, resection of spike onset, but not area of spike spread or the seizure onset zone, predicted outcome with positive predictive value of 79% and negative predictive value of 56% (P = 0.04). Spatiotemporal mapping of spike propagation reveals information flow from onset to areas of spread in epilepsy brain. Surgical resection of the spike onset disrupts the epileptogenic network and may render patients with drug resistant epilepsy seizure-free without having to wait for a seizure to occur during intracranial monitoring.

Ictal blinking triggered by isolated spikes as the only manifestation of seizures.

To describe blinking as the only manifestation of seizures from isolated focal and generalized cortical spikes and investigate the relationship between blinks and epileptic discharges. We measured the latency from the onset of spikes to the onset of blinks in two patients using electroencephalogram (EEG) and an electrooculogram (EOG), and calculated the median latency in both cases. We analyzed the latency from spike onset to the onset of additional specific eye movements, seen only in the second case. To determine the frequency of spontaneous blinks (not triggered by spikes), we defined a "control point" at 45 s following a random spike for the first case. We tested for statistically significant associations between latencies of blinks (Case 1) as well as between latencies of blinks and specific eye movements (Case 2). A total of 174 generalized spike-waves followed by a blink were analyzed in the first patient. Approximately 61% of the blinks occurred within 150-450 ms after the onset of the spike. Median latency for blinks following a spike was 294 ms compared to 541 ms for control blinks (p=.02). For the second patient, a total of 160 eye movements following a right occipito-parietal spike were analyzed. The median spike-blink latency in the second case was 497 milliseconds. Median latencies of spike onset to contralateral oblique eye movements with blink and left lateral eye movements were 648 and 655 milliseconds, respectively. Our study shows that isolated cortical spikes can induce epileptic seizures consisting exclusively of blinks. These findings emphasize the importance of careful EEG and EOG analysis to determine blinking as the only ictal phenomenon. We additionally describe a new technique to prove the temporal relationship between cortical discharges and a specific movement when, in addition to the movements triggered by a spike, the same movement is also spontaneously performed by the patient (in this case, blinking).

Fully-Automated Spike Detection and Dipole Analysis of Epileptic MEG Using Deep Learning.

Magnetoencephalography (MEG) is a useful tool for clinically evaluating the localization of interictal spikes. Neurophysiologists visually identify spikes from the MEG waveforms and estimate the equivalent current dipoles (ECD). However, presently, these analyses are manually performed by neurophysiologists and are time-consuming. Another problem is that spike identification from MEG waveforms largely depends on neurophysiologists' skills and experiences. These problems cause poor cost-effectiveness in clinical MEG examination. To overcome these problems, we fully automated spike identification and ECD estimation using a deep learning approach fully automated AI-based MEG interictal epileptiform discharge identification and ECD estimation (FAMED). We applied a semantic segmentation method, which is an image processing technique, to identify the appropriate times between spike onset and peak and to select appropriate sensors for ECD estimation. FAMED was trained and evaluated using clinical MEG data acquired from 375 patients. FAMED training was performed in two stages: in the first stage, a classification network was learned, and in the second stage, a segmentation network that extended the classification network was learned. The classification network had a mean AUC of 0.9868 (10-fold patient-wise cross-validation); the sensitivity and specificity were 0.7952 and 0.9971, respectively. The median distance between the ECDs estimated by the neurophysiologists and those using FAMED was 0.63 cm. Thus, the performance of FAMED is comparable to that of neurophysiologists, and it can contribute to the efficiency and consistency of MEG ECD analysis.

Can peak left ventricular activation time measured in aVL identify left bundle capture during left bundle branch area pacing?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Two main types of capture are observed during left bundle branch area pacing (LBBAP): LBB pacing (selective-LBBP or non-selective LBBP) and LV septal (LVS) capture. Several criteria are used to distinguish between both types. Methods Prospective study of patients who received LBBAP device for bradycardia or heart failure indications (bailed-out strategy). LBBP was defined if monopolar paced QRS had a right bundle branch conduction delay pattern, at least one of the following criteria: (a) Demonstration of LB potential with LB-local ventricular electrogram interval of 10–35 ms. (b) Demonstration of transition in QRS morphology from non-selective to selective LB capture or non-selective to LVS capture (sudden decrease in LVAT of 10 ms) with decrementing output. (c) Peak LV activation time time as measured in leads V5–V6 &amp;lt;80 ms. Patients not fulfilling criteria for LBBP were catalogued as LVS pacing. We analyzed the role that peak LVAT in the lead aVL (measured from the onset of the pacing spike to the peak of the R wave) had to discriminate between LBBP and LVS pacing and its correlation with LVAT measured in V5-V6. Results 154 consecutive LBBAP procedures were included. Success was achieved in 150 patients (97,4%). Mean age at implant was 79.4±9.3 years, native QRS duration was 118.7±29.4 ms, and LVEF was ≤ 40% in 16 (10,5%). A narrow (&amp;lt; 120 ms) QRS complex was present in 82 patients (53,2%) and LBBB was present in 21 patients. Indications for pacing were second- or third-degree AV block (n=57), slow AF (n=22), bifascicular or trifascicular block (n=12), sinus node disease (n=56) and need for resynchronization therapy (n=6). A Medtronic 3830-69 lead was implanted using a C-315-His sheath in all procedures. We did not perform His mapping to select the target delivery zone. LBBP was achieved in 117 patients (NSLBBP in 67 and SLBBP in 50) while LVS was achieved in the remaining 30 patients. Paced QRS duration after LBBAP was 115.3±14.7 ms, with a mean LVAT (measured at V5/V6) of 79.8±11.3 ms and mean LVAT in aVL of 83.6±14.6 ms. Left bundle potential was seen in 64 patients (44.4% of total population. LVAT in both V5/V6 and aVL was longer in LBBP patients compared to LVS patients (table 1). Accuracy of LVAT measured in aVL for the differential diagnosis of LBBP and LVS capture was good (AUC 84,6%). The diagnostically optimal value for discrimination among the two types of capture was 84 ms (sensitivity and specificity of 65.5% and 93.3%, respectively) (Panel A, figure 1). Moreover, ROC curve for discrimination between patients with LVAT in V5/V6&amp;lt;80 ms and &amp;gt;80 ms was also good (AUC 87.8%). A cut-off point for LVAT in aVL &amp;lt; 84 ms was also the diagnostically optimal value with a sensitivity and specificity of 80.2% and 80%, respectively). (Panel B, figure 1) Conclusions Peak LVAT measured in aVL lead might be a useful tool during LBBAP for differentiation between LBB capture and LVS capture.

Kisspeptin-13 prevented the electrophysiological alterations induced by amyloid-beta pathology in rat: Possible involvement of stromal interaction molecules and pCREB

Alzheimer's disease (AD) is a progressive neurological disease that slowly causing memory impairments with no effective treatment. We have recently reported that kisspeptin-13 (KP-13) ameliorates Aβ toxicity-induced memory deficit in rats. Here, the possible cellular impact of kisspeptin receptor activation in a rat model of the early stage AD was assessed using whole-cell patch-clamp recording from CA1 pyramidal neurons and molecular approaches. Compared to neurons from the control group, cells from the Aβ-treated group displayed spontaneous and evoked hyperexcitability with lower spike frequency adaptation. These cells had also a lower sag ratio in response to hyperpolarizing prepulse current delivered before a depolarizing current injection. Neurons from the Aβ-treated group exhibited short spike onset latency, lower rheobase and short utilization time compared with those in the control group. Furthermore, phase plot analysis of action potential showed that Aβ treatment affected the action potential features. These electrophysiological changes induced by Aβ were associated with increased expression of stromal interaction molecules (STIMs), particularly (STIM2) and decreased pCREB/CREB ratio. Treatment with KP-13 following Aβ injection into the entorhinal cortex, however, prevented the excitatory effect of Aβ on spontaneous and evoked neuronal activity, increased the latency of onset, enhanced the sag ratio, increased the rheobase and utilization time, and prevented the changes induced Aβ on spike parameters. In addition, the KP-13 application after Aβ treatment reduced the expression of STIMs and increased the pCREB/CREB ratio compared to those receiving Aβ treatment alone. In summary, these results provide evidence that activation of kisspeptin receptor may be effective against pathology of Aβ.

Mapping Propagation of Interictal Spikes, Ripples, and Fast Ripples in Intracranial EEG of Children with Refractory Epilepsy.

Studies on intracranial electroencephalography (icEEG) recordings of patients with drug resistant epilepsy (DRE) show that epilepsy biomarkers propagate in time across brain areas. Here, we propose a novel method that estimates critical features of these propagations for different epilepsy biomarkers (spikes, ripples, and fast ripples), and assess their common onset as a reliable biomarker of the epileptogenic zone (EZ). For each biomarker, an automatic algorithm ranked the icEEG electrodes according to their timing occurrence in propagations and finally dichotomized them as onset or spread. We validated our algorithm on icEEG recordings of 8 children with DRE having a good surgical outcome (Engel score = 1). We estimated the overlap of the onset, spread, and entire zone of propagation with the resection (RZ) and the seizure onset zone (SOZ). Spike and ripple propagations were seen in all patients, whereas fast ripple propagations were seen in 6 patients. Spike, ripple, and fast ripple propagations had a mean duration of 28.3 ± 24.3 ms, 38.7 ± 37 ms, and 25 ± 14 ms respectively. Onset electrodes predicted the RZ and SOZ with higher specificity compared to the entire zone for all three biomarkers (p<0.05). Overlap of spike and ripple onsets presented a higher specificity than each separate biomarker onset: for the SOZ, the onsets overlap was more specific (97.89 ± 2.36) than the ripple onset (p=0.031); for the RZ, the onsets overlap was more specific (98.48 ± 1.5) than the spike onset (p=0.016). Yet, the entire zone for spike and ripple propagations predicted the RZ with higher sensitivity compared to each biomarker's onset (or spread) (p<0.05). We present, for the first time, preliminary evidence from icEEG data that fast ripples propagate in time across large areas of the brain. The onsets overlap of spike and ripple propagations constitutes an extremely specific (but not sensitive) biomarker of the EZ, compared to areas of spread (and entire areas) in propagation.

Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson's Disease.

L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.

Electrophysiological and Morphological Features of Rebound Depolarization Characterized Interneurons in Rat Superficial Spinal Dorsal Horn.

Substantia gelatinosa (SG) neurons, which are located in the spinal dorsal horn (lamina II), have been identified as the “central gate” for the transmission and modulation of nociceptive information. Rebound depolarization (RD), a biophysical property mediated by membrane hyperpolarization that is frequently recorded in the central nervous system, contributes to shaping neuronal intrinsic excitability and, in turn, contributes to neuronal output and network function. However, the electrophysiological and morphological properties of SG neurons exhibiting RD remain unclarified. In this study, whole-cell patch-clamp recordings were performed on SG neurons from parasagittal spinal cord slices. RD was detected in 44.44% (84 out of 189) of the SG neurons recorded. We found that RD-expressing neurons had more depolarized resting membrane potentials, more hyperpolarized action potential (AP) thresholds, higher AP amplitudes, shorter AP durations, and higher spike frequencies in response to depolarizing current injection than neurons without RD. Based on their firing patterns and morphological characteristics, we propose that most of the SG neurons with RD mainly displayed tonic firing (69.05%) and corresponded to islet cell morphology (58.82%). Meanwhile, subthreshold currents, including the hyperpolarization-activated cation current (Ih) and T-type calcium current (IT), were identified in SG neurons with RD. Blockage of Ih delayed the onset of the first spike in RD, while abolishment of IT significantly blunted the amplitude of RD. Regarding synaptic inputs, SG neurons with RD showed lower frequencies in both spontaneous and miniature excitatory synaptic currents. Furthermore, RD-expressing neurons received either Aδ- or C-afferent-mediated monosynaptic and polysynaptic inputs. However, RD-lacking neurons received afferents from monosynaptic and polysynaptic Aδ fibers and predominantly polysynaptic C-fibers. These findings demonstrate that SG neurons with RD have a specific cell-type distribution, and may differentially process somatosensory information compared to those without RD.

Interictal spike localization for epilepsy surgery using magnetoencephalography beamforming

ObjectiveMagnetoencephalography (MEG) kurtosis beamforming is an automated localization method for focal epilepsy. Visual examination of virtual sensors, which are source activities reconstructed by beamforming, can improve performance but can be time-consuming for neurophysiologists. We propose a framework to automate the method and evaluate its effectiveness against surgical resections and outcomes. MethodsWe retrospectively analyzed MEG recordings of 13 epilepsy surgery patients who had one-year minimum post-operative follow-up. Kurtosis beamforming was applied and manual inspection was confined to morphological clusters. The region with the Maximum Interictal Spike Frequency (MISF) was validated against prospectively modelled sLORETA solutions and surgical resections linked to outcome. ResultsOur approach localized spikes in 12 out of 13 patients. In eight patients with Engel I surgical outcomes, beamforming MISF regions were concordant with surgical resection at overlap level for five patients and at lobar level for three patients. The MISF regions localized to spike onset and propagation modelled by sLORETA in two and six patients, respectively. ConclusionsAutomated beamforming using MEG can predict postoperative seizure freedom at the lobar level but tends to localize propagated MEG spikes. SignificanceMEG beamforming may contribute to non-invasive procedures to predict surgical outcome for patients with drug-refractory focal epilepsy.

Evaluation of Antioxidant Activities, Oxidation Enzymes, and Quality of Nano-Coated Button Mushrooms (Agaricus Bisporus) during Storage

Agaricus Bisporus is an edible button mushroom that is highly perishable with an extremely short shelf-life at ambient temperature. This work aims to evaluate some antioxidant activities, oxidation enzymes, and determine postharvest qualities of nano-coated mushrooms with the combination of chitosan (CHN) component during storage at 4 °C for (0, 3, 6, 9, and 12 days). Silica/CHN Film strongly delayed the mushroom respiratory spike onset and blocked carbon dioxide passage from inside to the outside, while Titanium/CHN Film (0.035 mmol s−1 kg−1) established the lowest O2 production rate and thiobarbituric acid reactive substances production (6.21 nmol g−1). Silica/CHN Film was mainly effectual for the polyphenol contents (0.39 g kg−1) and antioxidant activities (78.14% and 71.09%) for DPPH and ABTS+ radical scavenging activities, respectively. The results reported that Silica/CHN Film induced the highest (catalase and ascorbate peroxidase) activities, while Titanium/CHN Film recorded the highest (peroxidase and superoxide dismutase) activities of antioxidant enzymes. Besides, Titanium/CHN Film preserved relatively lower contents of hydrogen peroxide (22.40 µmol g−1) and hydroxyl radical (0.16 µmol g−1). In a word, nano-materials used in coating films such as titanium or even silica with the combination of CHN can directly reduce the cell degradation, oxidation processes and enhance the harvested horticultural crops.

Firing statistics in the bistable regime of neurons with homoclinic spike generation.

Neuronal voltage dynamics of regularly firing neurons typically has one stable attractor: either a fixed point (like in the subthreshold regime) or a limit cycle that defines the tonic firing of action potentials (in the suprathreshold regime). In two of the three spike onset bifurcation sequences that are known to give rise to all-or-none type action potentials, however, the resting-state fixed point and limit cycle spiking can coexist in an intermediate regime, resulting in bistable dynamics. Here, noise can induce switches between the attractors, i.e., between rest and spiking, and thus increase the variability of the spike train compared to neurons with only one stable attractor. Qualitative features of the resulting spike statistics depend on the spike onset bifurcations. This paper focuses on the creation of the spiking limit cycle via the saddle-homoclinic orbit (HOM) bifurcation and derives interspike interval (ISI) densities for a conductance-based neuron model in the bistable regime. The ISI densities of bistable homoclinic neurons are found to be unimodal yet distinct from the inverse Gaussian distribution associated with the saddle-node-on-invariant-cycle bifurcation. It is demonstrated that for the HOM bifurcation the transition between rest and spiking is mainly determined along the downstroke of the action potential-a dynamical feature that is not captured by the commonly used reset neuron models. The deduced spike statistics can help to identify HOM dynamics in experimental data.

An ultra-low power analog QRS-detection circuit for ambulatory ECG monitoring

In this paper, an ultra-low-power QRS-detection circuit is proposed which is suitable for wearable and implantable ECG-monitoring applications. Implementing the major part of the system in the analog-domain using current-mode circuits in the subthreshold region leads to an extremely low power consumption. The proposed circuit is based on calculating the energy of the derivative of the signal which follows by the onset spike detection method. Two low-pass filters with ultra-low cutoff frequencies of 6.45 Hz and 0.23 Hz are utilized in this method which are required for removing the high-frequency noise and estimating the required threshold for QRS-detection, respectively. The proposed algorithm is evaluated over the entire standard MIT-BIH arrhythmia database which results in a detection error rate of 1.46% with sensitivity and positive prediction of 99.17% and 99.36%, respectively. This QRS-detector circuit is implemented in 0.13 μm CMOS technology with a power supply of 1.2 V which consumes 31.5nW power and occupies 0.097 mm2 of silicon area. As the proposed circuit uses the analog ECG signal, there is no need to use an analog-to-digital converter which yields to further save in the area and power consumption of the entire system.

O1-045 MEG analysis of spike onset zone in various epileptogenic lesions

O1-045 MEG analysis of spike onset zone in various epileptogenic lesions

Interplay between channel and shot noise at the onset of spiking activity in neural membranes

The role played by ion channel noise and ion shot noise around the threshold conditions for spiking activity in biological membranes is studied by means of a stochastic model based on the Hodgkin–Huxley equations, considering membrane voltage-dependent gating channels for sodium and potassium cations, and leakage channels. Ion channel noise, that is, the noise linked to the random opening and closing of the ion channels, is included by means of Langevin sources. Ion shot noise, associated with the random passage of ions through the cell membrane, is considered by using the Gillespie’s method, in terms of the probabilities for different ions to cross the membrane. The threshold for spiking activity is reached by applying increasing values of an external excitation Iapp in a large membrane patch S, for which the strength of channel noise is insufficient for the onset of spikes in the absence of Iapp. On the other hand, since by decreasing S the strength of both noise sources increases, spiking activity is also achieved for small enough values of S when Iapp = 0. The noise behavior of this biological system is analyzed in terms of the autocorrelation function and the spectral density of the membrane voltage fluctuations. Even if ion shot noise is typically considered as negligible when other electrical sources of neural noise are taken into account, the results indicate that, particularly around the onset of instabilities, the signature of shot noise, by the interplay with channel noise, is evident in the spectral density of the membrane voltage fluctuations.

KCC2 antagonism and gabaergic synchronization in the entorhinal cortex in the absence of ionotropic glutamatergic receptor signalling

γ-Aminobutyric acid (GABA), which is released by interneurons, plays an active role in generating interictal epileptiform spikes during blockade of ionotropic glutamatergic signalling, but it remains unclear whether and how the K+-Cl− cotransporter 2 (KCC2) influences these paroxysmal events. Therefore, we employed tetrode recordings in the in vitro rat entorhinal cortex (EC) to analyze the effects of the KCC2 antagonist VU0463271 on 4-aminopyridine (4AP)-induced interictal spikes that were pharmacologically isolated by applying ionotropic glutamatergic receptor antagonists. After the addition of VU0463271, these interictal spikes continued to occur at similar rates as in control (i.e., during application of 4AP with ionotropic glutamatergic receptor antagonists) but were smaller and shorter. Despite the absence of ionotropic glutamatergic receptor signalling, both interneurons and principal cells increased their firing during interictal spikes. Moreover, we found that KCC2 antagonism increased interneuron firing but decreased principal cell firing during the interictal spike rising phase; in contrast, during the falling phase, interneuron firing decreased in the presence of VU0463271 while no change was observed in principal cell firing. Overall, our results show that KCC2 antagonism enhances interneuron excitability at the onset of interictal spikes generated by the EC neuronal networks during blockade of ionotropic glutamatergic transmission but disrupts later neuronal recruitment.