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Interictal 18F-fluorodeoxyglucose-PET (18F-FDG PET) is widely used in presurgical evaluation for epileptogenic zone (EZ) identification in patients with temporal lobe epilepsy. However, the area of PET hypometabolism is usually more extensive than the epileptogenic foci, providing approximate localization rather than precise. In this study, we evaluated the performance of 18F-FDG PET for classifying the EZs and the non-EZs using the radiomics features in addition to the hypometabolic features. The PET images of twelve patients with temporal lobe epilepsy were segmented into small cubes, which were labelled as EZs defined by the surgical resection areas or non-EZs. After extracting the radiomics features as well as the hypometabolic features of each cube, a support vector machine classifier was employed to classify each cube into EZ or non-EZ. The classifier performed well with the area under the curve (AUC) of $0.893 \pm 0.051$ , and using the combined features together got better performance than using the hypometabolic features only. The findings of this study merit further explorations to encourage the use of radiomics features in clinical decision for the EZ localization based on 18F-FDG PET.

Neuromodulation is a promising therapeutic alternative for epilepsy. We aimed to explore the efficacy and safety of cathodal transcranial current direct stimulation (ctDCS) on electroencephalographic functional networks in focal epilepsy.A sham-controlled, double-blinded, randomized study was conducted on 25 participants with focal epilepsy who underwent a 5-day, -1.0 mA, 20 min ctDCS, which targeted at the most active interictal epileptiform discharge (IED) region. We examined the electroencephalograms (EEGs) at baseline, immediately and at 4 weeks following ctDCS. The graph theory-based brain networks were established through time-variant partial directed coherence (TVPDC), and were calculated between each pair of EEG signals. The functional networks were characterized using average clustering coefficient, characteristic path length, and small-worldness index. The seizure frequencies, IEDs, graph-theory metrics and cognitive tests were compared.Preliminary findings indicated an IED reduction of 30.2% at the end of 5-day active ctDCS compared to baseline (p 0.10) and a significant IED reduction of 33.4% 4 weeks later (p 0.05). In terms of the EEG functional network, the small-worldness index significantly reduced by 3.5% (p 0.05) and the characteristic path length increased by 1.8% (p 0.10) at the end of the session compared to the baseline. No obvious change was found in the seizure frequency during follow-up (p 0.05). The Mini-Mental State Examination (MMSE) showed no difference between the active and sham groups (p 0.05). No severe adverse reactions were observed.In focal epilepsy, the 5-day consecutive ctDCS may potentially decrease the IEDs and ameliorate the EEG functional network, proposing a novel personalized therapeutic scenario for epilepsy.

Accurate localization of the epileptogenic zone (EZ) is crucial for refractory focal epilepsy patients to achieve freedom from seizures following epilepsy surgery. In this study, ictal stereo-electroencephalography data from 35 patients with refractory focal epilepsy were analyzed. Effective networks based on partial directed coherence were analyzed, and a gray level co-occurrence matrix was applied to extract the time-varying features of the in-degree. These features, combined with the single-channel signal time-frequency features, including approximate entropy and line length, were used to localize the EZ based on a cluster algorithm. For all seizure-free patients (n = 23), the proposed method was effective in identifying the clinical-EZ-contacts and clinical-EZ-blocks, with an F1-score of 62.47 % and 72.18 %, respectively. The sensitivity was 96.00 % for the clinical-EZ-block identification, which provided the information for the decision-making of clinicians, prompting clinicians to focus on the identified EZ-blocks and their nearby contacts. The agreement between the EZ identified by the proposed method and the clinical-EZ was worse for non-seizure-free patients (n = 12) than for seizure-free patients. Furthermore, our method provided better results than using only brain network or single-channel signal features. This suggests that combining these complementary features can facilitate more accurate localization of the EZ.

Localization of the epileptogenic zone (EZ) is essential for the successful surgical treatment of medically intractable epilepsy. In the present study, stereo-EEG (SEEG) recordings were obtained from seven patients underwent presurgical evaluation for treatment of intractable epilepsy. Partial directed coherence (PDC) analysis was applied to construct peri-ictal effective connectivity networks. The graphic measures, in-degree, out-degree and betweenness centrality, were evaluated to localize the EZ. A receiver operating characteristic (ROC) analysis was used to quantify the localization accuracy. We found that the in-degree coincided well with the EZ identified by epileptologists' visual inspection in all seven patients who had a significant improvement in seizure outcomes, however, the other two measures were effective only in some cases. Furthermore, in all seven patients the electrode contact with the highest in-degree was always located within the EZ identified by epileptologists' visual inspection. These results indicate that the graph theory is an effective method to localize the EZ when suitable graphic measures were chosen. Furthermore, the in-degree was the most effective measure among the three graphic measures in localizing the EZ when the PDC method was used.

Two new chromene derivatives, songaricachromenes A (1) and B (2), were isolated from Artemisia songarica, along with 10 known compounds (3–12). The structures and stereochemistry of the new compounds were elucidated by analyses of the NMR, MS, and electronic circular dichroism (ECD) data. All the isolates (1–12) were evaluated for their NO inhibitory effects on LPS-stimulated BV-2 microglial cells.

Oscillatory activity of retinal ganglion cell (RGC) has been observed in various species. It was reported such oscillatory activity is raised within large neural network and involved in retinal information coding. In the present research, we found an oscillation-like activity in ON–OFF RGC of bullfrog retina, and studied the mechanisms underlying the ON and OFF activities respectively. Pharmacological experiments revealed that the oscillation-like activity patterns in both ON and OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic inhibition is essential for generating them. At the meantime, such activities in the ON and OFF pathways showed different responses to several other applied drugs. The oscillation-like pattern in the OFF pathway was abolished by glycine receptor antagonist or gap junction blocker, whereas that in the ON pathway was not affected. Furthermore, the blockade of the ON pathway by metabotropic glutamate receptor agonist led to suppression of the oscillation-like pattern in the OFF pathway. These results suggest that the ON pathway has modulatory effect on the oscillation-like activity in the OFF pathway. Therefore, the mechanisms underlying the oscillation-like activities in the ON and OFF pathways are different: the oscillation-like activity in the ON pathway is likely caused by GABAergic amacrine cell network, while that in the OFF pathway needs the contributions of GABAergic and glycinergic amacrine cell network, as well as gap junction connections.

Two new disesquiterpenoids (1 and 2) and 11 new (3–13) and 10 known (14–23) sesquiterpenoids were isolated from the whole plants of Artemisia freyniana. Their structures were elucidated by spectroscopic data analysis and comparison with published NMR data. The absolute configurations of the new isolates (1–13) were assigned based on single-crystal X-ray diffraction data and comparison of the experimental and calculated ECD data. The eremophilane derivatives 8 and 9 possess an unprecedented 2-isopropyl-3,7,7a-trimethyl-2,4,5,6,7,7a-hexahydro-1H-indene scaffold, and a putative biosynthetic pathway for these compounds is proposed. Compounds 4, 5, and 9 exhibited inhibitory effects against LPS-stimulated nitric oxide (NO) production in RAW 264.7 macrophage cells with IC50 values of 10.8, 12.6, and 11.7 μM, respectively.

Epilepsy has been considered as a network-level disorder characterized by recurrent seizures, which result from network reorganization with evolution of synchronization. In this study, the brain networks were established by calculating phase synchronization based on electrocorticogram (ECoG) signals from eleven refractory epilepsy patients. Results showed that there was a significant increase of synchronization prior to seizure termination and no significant difference of the transitions of network states among the preseizure, seizure, and postseizure periods. Those results indicated that synchronization might participate in termination of seizures, and the network states transitions might not dominate the seizure evolution.

Oscillations in intracellular free Ca(2+) concentration ([Ca(2+)]i) have been observed in a variety of cell types. In the present study, we constructed a mathematical model to simulate the caffeine-induced [Ca(2+)]i oscillations based on experimental data obtained from isolated type I horizontal cell of carp retina. The results of model analysis confirm the notion that the caffeine-induced [Ca(2+)]i oscillations involve a number of cytoplasmic and endoplasmic Ca(2+) processes that interact with each other. Using this model, we evaluated the importance of store-operated channel (SOC) in caffeine-induced [Ca(2+)]i oscillations. The model suggests that store-operated Ca(2+) entry (SOCE) is elicited upon depletion of the endoplasmic reticulum (ER). When the SOC conductance is set to 0, caffeine-induced [Ca(2+)]i oscillations are abolished, which agrees with the experimental observation that [Ca(2+)]i oscillations were abolished when SOC was blocked pharmacologically, verifying that SOC is necessary for sustained [Ca(2+)]i oscillations.

Retinal ganglion cells (RGCs) exhibit adaptive changes in response to sustained light stimulation, which include decrease in firing rate, tendency to shrink in receptive field (RF) size and reduction in synchronized activities. Gamma-aminobutyric acid-ergic (GABAergic) pathway is an important inhibitory pathway in retina. In the present study, the effects of GABAergic pathway on the contrast adaptation process of bullfrog RGCs were studied using multi-electrode recording technique. It was found that the application of bicuculline (BIC), a gamma-aminobutyric acid A (GABAA) receptor antagonist, caused a number of changes in the RGCs’ response characteristics, including attenuation in adaptation-dependent firing rate decrease and the adaptation-dependent weakening in synchronized activities between adjacent neuron-pairs, whereas intensified the adaptation-dependent RF size shrinkage. These results suggest that GABAA receptors are involved in the modulation of the firing activity and synchronized activities in contrast adaptation process of the RGCs, whereas the adaptation-related RF property changes involve more complicated mechanisms.

Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg2+ or high-K+ artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed. The Na+-K+-2Cl- cotransporter 1 (NKCC1) blocker, bumetanide, was applied to test its effect upon epileptiform discharges in low-Mg2+ model. The effect of N-methyl-D-aspartate receptors (NMDARs) antagonist, D-AP5, upon the epileptiform discharges in high-K+ model was examined. We found that the neonatal subiculum not only relayed epileptiform discharges emanating from the hippocampus proper, but also initiated epileptiform discharges (interictal- and ictal-like discharges) independently. The latency to onset of the first epileptiform discharge initiated in the subiculum was similar to that initiated in the hippocampus proper. Bumetanide efficiently blocked seizures in the neonatal hippocampus proper, but was less effectively in suppressing seizures initiated in the subiculum. In high-K+ model, D-AP5 was more effective in blocking seizures initiated in the subiculum than that initiated in the hippocampus proper. Furthermore, Western blotting analysis showed that NKCC1 expression was lower in the subiculum than that in the hippocampus proper, whereas the expression of NMDAR subunits, NR2A and NR2B, was higher in the subiculum than that in the hippocampus proper. Our results revealed that the subiculum was a potential site of ictogenesis in neonatal seizures and possessed similar seizure susceptibility to the hippocampus proper. GABAergic excitation resulting from NKCC1 may play a less dominant role during ictogenesis in the subiculum than that in the hippocampus proper. The subicular ictogenesis may be related to the glutamatergic excitation mediated by NMDARs.

A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.

In the retina, the firing behaviors that ganglion cells exhibit when exposed to light stimuli are very important due to the significant roles they play in encoding the visual information. However, the detailed mechanisms, especially the intrinsic properties that generate and modulate these firing behaviors is not completely clear yet. In this study, 2 typical firing behaviors—i.e., tonic and phasic activities, which are widely observed in retinal ganglion cells (RGCs)—are investigated. A modified computational model was developed to explore the possible ionic mechanisms that underlie the generation of these 2 firing patterns. Computational results indicate that the generation of tonic and phasic activities may be attributed to the collective actions of 2 kinds of adaptation currents, i.e., an inactivating sodium current and a delayed-rectifier potassium current. The concentration of magnesium ions has crucial but differential effects in the modulation of tonic and phasic firings, when the model neuron is driven by N-methyl-D-aspartate (NMDA) -type synaptic input instead of constant current injections. The proposed model has robust features that account for the ionic mechanisms underlying the tonic and phasic firing behaviors, and it may also be used as a good candidate for modeling some other firing patterns in RGCs.

Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells' ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information about stimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.

Epilepsy is growingly considered as a brain network disorder. In this study, epileptiform discharges were induced by low-Mg2+ in mouse entorhinal cortex-hippocampal slices, and recorded with a micro-electrode array. Dynamic effective network connectivity was constructed by calculating the time-variant partial directed coherence (tvPDC) of signals. We proposed a novel approach to track the state transitions of epileptic networks over time, and characterized the network topology by using graphical measures. We found that the hub nodes with high degrees in the network coincided with the epileptogenic zone in previous electrophysiological findings. Two consecutive states with distinct network topologies were identified during the ictal-like discharges. The small-worldness remained at a low level at the first state but increased significantly at the second state. Our results indicate the ability of tvPDC to capture the causal interaction between multi-channel signals important in indentifying the epileptogenetic zone. Moreover, the evolution of network states extends our knowledge of the network drivers for the initiation and maintenance of ical activity, and suggests the practical value of our network clustering approach.

Objectives: Accurate localization of epileptogenic zones (EZs) is essential for successful surgical treatment of refractory focal epilepsy. The aim of the present study is to investigate whether a dynamic network connectivity analysis based on stereo-electroencephalography (SEEG) signals is effective in localizing EZs. Methods: SEEG data were recorded from seven patients who underwent presurgical evaluation for the treatment of refractory focal epilepsy and for whom the subsequent resective surgery gave a good outcome. A time-variant multivariate autoregressive model was constructed using a Kalman filter, and the time-variant partial directed coherence was computed. This was then used to construct a dynamic directed network model of the epileptic brain. Three graph measures (in-degree, out-degree, and betweenness centrality) were used to analyze the characteristics of the dynamic network and to find the important nodes in it. Results: In all seven patients, the indicative EZs localized by the in-degree and the betweenness centrality were highly consistent with the clinically diagnosed EZs. However, the out-degree did not indicate any significant differences between nodes in the network. Conclusions: In this work, a method based on ictal SEEG signals and effective connectivity analysis localized EZs accurately. The results suggest that the in-degree and betweenness centrality may be better network characteristics to localize EZs than the out-degree.

Objective It has been shown that low-intensity ultrasound (LIUS) can suppress seizures in some laboratory studies. However, the mechanism of the suppression effect of LIUS remains unclear. The goal of this study is to investigate the modulation effects of focused LIUS on epileptiform discharges in mouse hippocampal slices as well as the underlying mechanism. Approach Epileptiform discharges in hippocampal slices of 8 d-old mice were induced by low-Mg2+ artificial cerebrospinal fluid and recorded by a micro-electrode array in vitro. LIUS was delivered to hippocampal slices to investigate its modulation effects on epileptiform discharges. Pharmacological experiments were conducted to study the mechanism of the modulation effects. Main results LIUS suppressed the amplitude, rate and duration of ictal discharges. For inter-ictal discharges, LIUS suppressed the amplitude but facilitated the rate. LIUS suppressed the spontaneous spiking activities of pyramidal neurons in CA3, and the suppression effect was eliminated by Kaliotoxin. The suppression effect of LIUS on epileptiform discharges was weakened when the perfusion was mixed with Kaliotoxin. Significance Those findings demonstrate that LIUS suppresses the epileptiform discharges in 8 d-old mouse hippocampal slices and that its suppression effect can mainly attributed to the activation of mechanosensitive Kv1.1 channels.

Synchronized activities among retinal ganglion cells (RGCs) via gap junctions can be increased by exogenous dopamine (DA). During DA application, single neurons' firing activities become more synchronized with its adjacent neighbors. One intriguing question is how the enhanced spatial synchronization alters the temporal firing structure of single neurons. In the present study, firing activities of bullfrog's dimming detectors in response to binary pseudo-random checker-board flickering were recorded via a multi-channel recording system. DA was applied in the retina to modulate synchronized activities between RGCs, and the effect of DA on firing activities of single neurons was examined. It was found that, during application of DA, synchronized activities between single neuron and its neighboring neurons was enhanced. At the meantime, the temporal structures of single neuron spike train changed significantly, and the temporal correlation in single neuron's response decreased. The pharmacological study results indicated that the activation of D1 receptor might have effects on gap junction permeability between RGCs. Our results suggested that the dopaminergic pathway participated in the modulation of spatial and temporal correlation of RGCs' firing activities, and may exert critical effects on visual information processing in the retina.

In vertebrate visual system, retina is the first stage for visual information processing. Retinal ganglion cells are the only output neurons of the retina, and their firing activities are dependent on visual stimuli. Retinal ganglion cells can effectively encode visual information via various manners, such as firing rate, temporal structure of spike trains, and concerted activity, etc. Adaptation is one of the basic characteristics of the nervous system, which enables retinal neurons to encode stimuli under a wide variety of natural conditions with limited range in their output. This article reviews the recent studies focused on the coding properties and adaptation of retinal ganglion cells. Relevant issues about dynamical adjustment of coding strategies of retinal ganglion cells in response to different visual stimulation, as well as physiological property and function of adaptation are discussed.

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1~5). The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study.(1)High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2.(2)In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells’ firing activities, while little change was induced in the first peak. Co-application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells.

Spike sorting is the mandatory first step in analyzing multiunit recording signals for studying information processing mechanisms within the nervous system. Extracellular recordings usually contain overlapped spikes produced by a number of neurons adjacent to the electrode, together with unknown background noise, which in turn induce some difficulties in neural signal identification. In this paper, we propose a robust method to deal with these problems, which employs an automatic overlap decomposition technique based on the relaxation algorithm that requires simple fast Fourier transforms. The performance of the presented system was tested at various signal-to-noise ratio levels based on synthetic data that were generated from real recordings.

The conformational analysis of high-density poly(ethylene) (HDPE) during the melting and crystallization processes has been performed by the aid of the time-reserved Fourier transform infrared spectroscopy and multivariate analysis technique. Upon heating, the conformational transition of HDPE takes place, gradually, due to the restraint of crystal lattice, and various conformational transformations can be discerned clearly. However, during the cooling process, HDPE crystallizes very quickly and only one major conformational transition occurs in the crystallization process. The comparison of conformational changes during the melting and crystallization processes exhibits that although the polymer crystallization is the reverse process of polymer melting, there still exist some obvious differences in the conformational transformation between them. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4835–4841, 2006

The thermal degradation of syndiotactic polypropylene (sPP) and the influence of stereoregularity on the thermal degradation behaviour have been studied by in situ Fourier transform infrared (FTIR) spectroscopy. With the aid of the time-resolved FTIR, the conventional kinetic parameters, such as the degradation activation energy ΔE and the degradation factor n, can be calculated. The experimental results show that sPP decomposes by random chain scissions. More importantly, the difference of degradation activation energy from some characteristic absorption bands shows that the thermal degradation of sPP is a multi-step process, which is further confirmed by the principal components analysis (PCA). Comparing with isotactic polypropylene (iPP), the main chain of sPP is more flexible, therefore the thermal stability of sPP is much higher than iPP.

A new method for spike sorting is proposed which partly solves the overlapping problem. Principal component analysis and subtractive clustering techniques are used to estimate the number of neurons contributing to multi-unit recording. Spike templates (i.e. waveforms) are reconstructed according to the clustering results. A template-matching procedure is then performed. Firstly all temporally displaced templates are compared with the spike event to find the best-fitting template that yields the minimum residue variance. If the residue passes the χ 2 -test, the matching procedure stops and the spike event is classified as the best-fitting template. Otherwise the spike event may be an overlapping waveform. The procedure is then repeated with all possible combinations of two templates, three templates, etc. Once one combination is found, which yields the minimum residue variance among the combinations of the same number of component templates and makes the residue pass the χ 2 -test, the matching procedure stops. It is unnecessary to check the remaining combinations of more templates. Consequently, the computational effort is reduced and the over-fitting problem can be partly avoided. A simulated spike train was used to assess the performance of the proposed method, which was also applied to a real recording of chicken retina ganglion cells.