High-Frequency Oscillations Detected in Epileptic Networks Using Swarmed Neural-Network Features

Localizing epileptic networks is a central challenge in guiding epilepsy surgery, deploying antiepileptic devices, and elucidating mechanisms underlying seizure generation. Recent work from our group and others suggests that high-frequency epileptic oscillations (HFEOs) arise from brain regions constituting epileptic networks, and may be important to seizure generation. HFEOs are brief 50–500 Hz pathologic events measured in intracranial field and unit recordings in patients with refractory epilepsy. They are challenging to detect due to low signal to noise ratio, and because they occur in multiple channels with great frequency. Their morphology is also variable and changes with distance from intracranial electrode contacts, which are sparsely placed for patient safety. Thus reliable, automated methods to detect HFEOs are required to localize and track seizure generation in epileptic networks. We present a novel method for mapping the temporal evolution of these oscillations in human epileptic networks. The technique combines a particle swarm optimization algorithm with a neural network to create features that robustly detect and track HFEOs in human intracranial EEG (IEEG) recordings. We demonstrate the algorithm’s performance on IEEG data from six patients, one pediatric and five adult, and compare it to an existing method for detecting high-frequency oscillations.     

A new therapy for refractory partial epilepsy: Current shunt

A large number of epileptic patients suffer from refractory epilepsy, despite optimal treatment; thus these patients require new therapeutic approaches. Focal seizure activity is typically initiated in a fixed and localized region, which subsequently spreads to neighboring regions or more distant areas. At the initial onset of a seizure, the epileptic discharge will generate a relatively high voltage in seizure focus, and the discharge subsequently spreads to other relatively low-voltage regions. However, it is unknown whether seizure can be controlled through current shunt using a conduction microelectrode to conduct the epileptic discharge with a relatively high voltage in the seizure focus outside the brain. The current therapies for epilepsy, including drugs, resective surgery and neuromodulation, focus on inhibiting abnormal excessive or synchronous neuronal activity to control seizures; thus, the basic mechanism underlying these therapies is “inhibition”. In contrast, we proposed a “conduction” mechanism, whereby a current shunt with conduction electrode is used to control seizures. To our knowledge, this therapeutic strategy has not been previously reported, and we propose that this approach might be an alternative choice for the treatment of refractory partial epilepsy in the future.     

大鼠癫痫发作可预测性的研究

癫痫是一种常见的神经系统疾病,其长期反复发作,使患者身心不断遭受伤害.若能提前预测到癫痫的发作,则可以使患者及时采取措施进行预防和保护.在癫痫发作预测研究中,动物模型可以提供丰富的样本,验证算法可行性,揭示癫痫发作的规律.本文制作了癫痫大鼠模型并建立了数据采集系统.利用同步性和复杂度两种非线性特征,对12次癫痫大发作进行分析,发现癫痫发作前同步性特征呈下降或上升趋势,复杂度特征则呈与同步性相反的变化趋势.这种变化在发作前几分钟出现,分析结果验证了癫痫发作的可预测性.     

Dynamics of evoked local field potentials in the hippocampus of epileptic rats with spontaneous seizures

A change in neuronal network excitability within the hippocampus is one of the hallmarks of temporal lobe epilepsy (TLE). In the dentate gyrus (DG), however, neuronal loss and mossy fiber sprouting are associated with enhanced inhibition rather than progressive hyperexcitability. The aim of this study was to investigate how alterations in excitability take place in association with spontaneous seizures expressed in the DG before, during, and after a seizure. For this purpose, we used freely moving rats that had developed spontaneous seizures after a kainate-induced status epilepticus (SE). Continuous EEG was recorded in the DG during several days along with local field potentials (LFPs) that were evoked every 15-30 s by applying paired-pulse stimuli to the angular bundle. Input-output relations showed increased paired pulse depression in epileptic compared with control rats, suggesting a rather strong inhibition in the DG during the interictal state. A characteristic pattern of changes in intrinsic excitability was observed during the ictal period: an increase in the population spike (PS) amplitude, mostly during the early phase of a seizure and often followed by a decrease of the main evoked potential amplitude. The paired-pulse extracellular postsynaptic potential (fEPSP) ratio increased during the seizure and did slowly recover to preictal levels after the seizure ended. Although clear changes in excitability occurred during and after seizure activity, changes of LFP parameters were more subtle before seizure onset; a significant reduction of LFP and PS amplitudes was observed that started 1-2 min in advance in approximately 33% of the cases; in approximately 18%, an increase of LFP/PS amplitude was observed; in the other cases, no significant change was observed. Taken together, these results provide evidence that, in this experimental model, DG physiology is more likely to follow the already ongoing seizure activity rather than to contribute to its generation.     

Investigation of the neuronal aggregate generating seizures in the rat tetanus toxin model of epilepsy

A key question in epilepsy is the organization and size of the neuronal networks necessary for generating seizures. Hypotheses include: a single focal neuronal network drives seizure discharges across the brain, which may or may not be identical with the circuits that generate interictal spikes; or multiple neuronal networks link together in re-entrant loops or other long-range networks. It remains unclear whether any of these hypotheses apply to spontaneous seizures in freely moving animals. We used the tetanus toxin chronic model of epilepsy to test the different predictions made by each hypothesis about the propagation and interaction of epileptic discharges during seizures. Seizures could start in either the injected or noninjected dorsal hippocampus, suggesting that seizures have multifocal onsets in the tetanus toxin model. During seizures, individual bursts propagated in either direction, both between the right and left dorsal hippocampi, and between CA3 and the dentate gyrus in the same hippocampus. These findings argue against one site "driving" seizures or seizures propagating around a limbic loop. Specifically, the side leading each burst switched a median of three times during the first 20 s of a seizure. Analysis of bursts during seizures suggested that the network at each recording site acted like a neuronal oscillator. Coupling of population spikes in right and left CA3 increased during the early part of seizures, but the cross-correlation of their whole-discharge waveforms changed little over the same period. Furthermore, the polarity of the phase difference between population spikes did not follow the phase difference for complete discharges. We concluded that the neuronal aggregate necessary for seizures in our animals comprises multiple spatially distributed neuronal networks and that the increased synchrony of the output (population spike firing) of these networks during the early part of seizures may contribute to seizure generation.     

High-frequency oscillations (HFOs) in clinical epilepsy

Epilepsy is one of the most frequent neurological diseases. In focal medically refractory epilepsies, successful surgical treatment largely depends on the identification of epileptogenic zone. High-frequency oscillations (HFOs) between 80 and 500Hz, which can be recorded with EEG, may be novel markers of the epileptogenic zone. This review discusses the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. HFOs are clearly linked to the seizure onset zone, and the surgical removal of regions generating them correlates with a seizure free post-surgical outcome. Moreover, HFOs reflect the seizure-generating capability of the underlying tissue, since they are more frequent after the reduction of antiepileptic drugs. They can be successfully used in pediatric epilepsies such as epileptic spasms and help to understand the generation of this specific type of seizures. While mostly recorded on intracranial EEGs, new studies suggest that identification of HFOs on scalp EEG or magnetoencephalography (MEG) is possible as well. Thus not only patients with refractory epilepsies and invasive recordings but all patients might profit from the analysis of HFOs. Despite these promising results, the analysis of HFOs is not a routine clinical procedure; most results are derived from relatively small cohorts of patients and many aspects are not yet fully understood. Thus the review concludes that even if HFOs are promising biomarkers of epileptic tissue, there are still uncertainties about mechanisms of generation, methods of analysis, and clinical applicability. Large multicenter prospective studies are needed prior to widespread clinical application.     

基于C-FFuzzyEn的神经电生理信号同步性分析

基于传统互模糊熵,结合分数阶微积分提出分数阶互模糊熵（C-FFuzzyEn）,并基于该算法分析混沌耦合系统的同步性,进行健康对照者和癫痫患者不同脑区脑电信号的耦合性对比。结果表明,与传统互模糊熵相比,C-FFuzzyEn提高了不同耦合度模型的区分能力;与健康对照者相比,癫痫患者在癫痫发作时不同通道脑电信号之间C-FFuzzyEn较小,与癫痫发作时各神经元同步放电现象相吻合;相比互模糊熵,C-FFuzzyEn区分健康对照者与癫痫患者脑区之间脑电信号同步性的效果更好。C-FFuzzyEn可应用于脑电信号等神经电生理信号的同步性分析。     

Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals

Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.     

癫痫发作的神经电生理特征

癫痫是以反复发作的阵发性神经性或行为表现为特征的脑功能失调,其原因是大群神经元的不正常同步性过度放电。癫痫的发病率占总人群的0.5%-2%[1],癫痫不是单一疾病,原因不一,反映了后天与遗传的多因素病症。多数癫痫综合症可以划分为两种基本类别[2]:部分性(partial)和全身性(generalized)。部分性发作发生在大脑的局部区域内,所以又称为局灶性癫痫,而全身性发作则出现在整个前脑(至少在EEG水平)[2]。有关癫痫发作的可能机制已被广泛研究,从神经元、突触、神经元组成的网络,到解剖、生理、生化、遗传和分子生物学,都积累了大量的文献[2],…     

获得性癫癎失语综合征5例报告

目的：研究获得性癫癎失语综合征（Landau-Kleffner syndrome,LKS）的临床、脑电图（EEG）特征、治疗反应和远期预后。方法：对5例LKS患儿的临床表现、EEG特点和临床疗效进行观察,并结合文献进行探讨。结果：起病年龄为4～12岁。5例患儿均有不同类型的癫癎发作,伴有进行性失语,其中1例智力明显低下。5例均有EEG异常,其中3例有颞区局限性棘慢波发放。癫癎发作均可用抗癫癎药物控制。经皮质激素治疗,失语有改善。随访癫癎发作控制均良好,但语言恢复较正常差,EEG癎样放电好转。结论：LKS是一种以获得性失语和癫癎发作两大症状为主要临床表现的儿童时期癫癎性脑病。失语表现为听觉失认,多伴有其他精神行为异常。EEG常见颞区的局限性癎样放电,睡眠期常泛化至全导联,并可呈持续发放。抗癫癎药物可控制癫癎发作,但对失语疗效不佳。早期应用足量皮质激素治疗可明显改善失语情况。EEG及癫癎发作转归良好,但常遗留语言障碍。     

癫痫发作类型与EEG的相关性

目的：分析各种发作类型癫痫及其与脑电图（EEG）表现的关系。方法：对352例确诊癫痫患者行规范的病史询问及长程EEG监测（描记时间10～15h）,并按照1981年ILAE分类和名词委员会推荐的癫痫发作的分类方案进行发作症状的分类,按照1989年II,AE推荐的癫痫和癫痫综合征的分类作出诊断,分析其发作类型和EEG之间的相关性。结果：在352例中,EEG异常246例,异常率为69．9％,24例（6．8％）记录到临床发作。EEG异常率与发作频率相关,每月发作大于4次者较每月发作少于4次者EEG异常率显著升高（P=0．014）。部分性发作和全面性发作的患者异常率比较差异无显著意义（P=0．929）,但前者更多表现为EEG局限性异常（P=0．014）。结论：规范的长程EEG检查异常率较高,EEG异常率与发作频率相关,不同癫痫发作类型患者的EEG表现有差异。     

A Novel Spatiotemporal Analysis of Peri-Ictal Spiking to Probe the Relation of Spikes and Seizures in Epilepsy

The relation between epileptic spikes and seizures is an important but still unresolved question in epilepsy research. Preclinical and clinical studies have produced inconclusive results on the causality or even on the existence of such a relation. We set to investigate this relation taking in consideration seizure severity and spatial extent of spike rate. We developed a novel automated spike detection algorithm based on morphological filtering techniques and then tested the hypothesis that there is a pre-ictal increase and post-ictal decrease of the spatial extent of spike rate. Peri-ictal (around seizures) spikes were detected from intracranial EEG recordings in 5 patients with temporal lobe epilepsy. The 94 recorded seizures were classified into two classes, based on the percentage of brain sites having higher or lower rate of spikes in the pre-ictal compared to post-ictal periods, with a classification accuracy of 87.4%. This seizure classification showed that seizures with increased pre-ictal spike rate and spatial extent compared to the post-ictal period were mostly (83%) clinical seizures, whereas no such statistically significant (α = 0.05) increase was observed peri-ictally in 93% of sub-clinical seizures. These consistent across patients results show the existence of a causal relation between spikes and clinical seizures, and imply resetting of the preceding spiking process by clinical seizures.     

老年人迟发性癫Xian发作的临床及脑电图分析

目的：探讨老年人迟发性癫Xian发作的临床及脑电图特点。方法：回顾性分析80例老年人迟发性癫Xian的临床及脑电图资料。结果：癫Xian发作的可能因为脑血管病41例（脑梗死30例、脑出血11例）,脑肿瘤19例,脑外伤4例,脑萎缩8例。癫Xian发作的类型为全身强直阵挛发作48例;强直阵挛发作持续状态2例,失神发作6例,单纯运动性发作17例,单纯体感性发作7例。脑电图正常7例,异常73例。异常脑电图主要表现为弥漫性慢波活动22例,局限于一侧半球的慢波活动34例,散在或阵发性棘波、尖波或棘慢、尖慢综合波49例。结论：脑血管病（脑梗死、脑出血）、脑肿瘤是老年迟发性癫Xian发作的主要原因。癫Xian发作以全身强直阵挛发作为主。脑电图异常率高,主要表现为在弥漫性慢波活动基础上出现癫Xian样放电。     

Dynamical intrinsic functional architecture of the brain during absence seizures

Epilepsy is characterized by recurrent and temporary brain dysfunction due to discharges of interconnected groups of neurons. The brain of epilepsy patients has a dynamic bifurcation that switches between epileptic and normal states. The dysfunctional state involves large-scale brain networks. It is very important to understand the network mechanisms of seizure initiation, maintenance, and termination in epilepsy. Absence epilepsy provides a unique model for neuroimaging investigation on dynamic evolutions of brain networks over seizure repertoire. By using a dynamic functional connectivity and graph theoretical analyses to study absence seizures (AS), we aimed to obtain transition of network properties that account for seizure onset and offset. We measured resting-state functional magnetic resonance imaging and simultaneous electroencephalography (EEG) from children with AS. We used simultaneous EEG to define the preictal, ictal and postictal intervals of seizures. We measured dynamic connectivity maps of the thalamus network and the default mode network (DMN), as well as functional connectome topologies, during the three different seizure intervals. The analysis of dynamic changes of anti-correlation between the thalamus and the DMN is consistent with an inhibitory effect of seizures on the default mode of brain function, which gradually fades out after seizure onset. Also, we observed complex transitions of functional network topology, implicating adaptive reconfiguration of functional brain networks. In conclusion, our work revealed novel insights into modifications in large-scale functional connectome during AS, which may contribute to a better understanding the network mechanisms of state bifurcations in epileptogenesis.     

利用广义复杂度对癫痫病发作进行预测的方法研究

目的：通过用广义复杂度的运算方法,分析癫痫病患者发病期间的脑电图,计算出这一段脑电图数据的复杂度,通过对复杂度数据的分析,对癫痫病的发作进行预测。进而提高癫痫病患者的生活质量,降低癫痫病患者的生命危险。方法：将癫痫病发病的脑电图的图像信号还原成数字信号,计算出该数字信号各个区间的广义复杂度值。得出癫痫病发病前脑电图数据复杂度的变化状态,对癫痫病患者发病进行预测。结果：计算出21名癫痫病患者在发病前后共一个小时的脑电图数字信号的广义复杂度值,通过观察21名癫痫病患者在癫痫病发病期间的脑电图的数字信号的广义复杂度变化情况,对癫痫病的发作进行预测（对2l名病人癫痫病发作的数据进行预测研究,平均准确率可达94.3%）。结论：本文提出了一种基于广义复杂度的癫痫发作预测方法,通过对21名癫痫病患者的脑电图信号的实验和计算,结果表明,该方法可以有效地预测到癫痫发作。     

癫癎发作后症状及脑电图分析

目的:探讨癫发作后常见症状的临床特征及在癫发作鉴别诊断中的作用。方法:选择癫患者50例,非癫性发作患者30例,分析发作后症状及脑电图表现。结果:38例癫患者和4例非癫患者发作后头痛、疲劳、嗜睡;脑电图(EEG)第一次检查异常38例,第二次异常44例,非癫发作后EEG异常8例。结论:癫患者有发作后症状,对癫的诊断有非常重要的价值。     

后头部癫癎发作症状学与头皮脑电图学分析

目的：研究后头部癫癎（PCE）患者发作症状学及头皮脑电图学（EEG）特点,结合神经影像学探讨PCE诊断要点。方法：回顾性分析在清华大学玉泉医院神经外科5病区（癫癎研究中心）就诊的22例PCE患者的81次发作,分析发作症状学、发作间期与发作期头皮EEG及神经影像学特点,总结诊断要点。结果：22例患者中10例存在影像学异常,后头部发作容易传播而表现为额叶的症状（姿势性不对称强直阵挛等）或颞叶内侧症状（口咽部或肢体自动症）而导致错误的诊断,先兆常常提示发作起源部位,头皮EEG发作间期及发作期往往不能提供明确或正确的信息。结论：PCE发作容易传播而表现为额叶或颞叶内侧症状而导致错误的诊断,先兆常常有助于正确诊断。     

基于自适应多尺度脑功能连接的局灶性癫痫发作检测方法研究

利用长时程脑电图检测癫痫发作是临床中较为广泛的应用,然而这项工作乏味、耗时,且很大程度上依赖于临床医生的自身经验和主观判断,准确性和可重复性也较低。针对长时程脑电图检测癫痫中存在的问题,提出一种基于自适应多尺度脑功能连接的癫痫发作检测方法(AMBFC),并选取10例局灶性癫痫患者的发作期和非发作期的样本作为研究对象。首先在一个滑动时间窗内,通过多元经验模态分解(MEMD)提取19通道脑电信号的7个本征模函数(IMF)分量及残差;然后建立多变量自回归(MVAR)模型,利用有向传递函数(DTF)提取流出信息强度,进行特征组合,并通过主成分分析(PCA)降维保留原始特征数目的85%;最后经代价敏感支持向量机(CSVM)分类区分发作期和非发作期脑电,并通过五重交叉验证进行癫痫发作检测算法的效果评价。结果表明,AMBFC算法检测脑电癫痫发作得到的平均准确率为98.6%,精确率为81.9%,召回率为81.4%,F2值为0.80。与各IMF分量、DTF-CSVM算法等检测结果相比,AMBFC算法更具有优越性。有望应用于长时程脑电的实时监测。     

癫癎发作早期Video-EEG监测的临床价值

目的 :探讨Video -EEG监测癫发作早期脑电变化的临床应用价值。方法 :对 96例临床确诊的癫患者进行发作早期Video -EEG监测并分析其结果。结果 :共监测到 3 2例癫发作(3 3 % ) ,其中全身性癫 4例 ;颞叶癫 16例 ,颞外癫 12例。发作早期脑电异常主要分快活动、慢活动及快慢混合活动三大类。根据发作早期脑电变化 ,2 3例 (72 % )作出定位诊断。结论 :癫发作早期脑电图脑电变化对致灶的定位 (定侧 )诊断有重要价值