Localization of primary auditory cortex in humans by magnetoencephalography

Brief auditory stimuli activate the primary auditory cortex (PAC) earlier than any other cortical area so, within a certain latency range, the PAC is the only cortical source contributing to the auditory evoked field (AEF). Nevertheless, there is no AEF component specific to PAC that can be reliably detected in all individuals. The present study suggests that a peak in the first temporal derivative of the magnetic field at about 20 ms (dP20m) is a genuine correlate of PAC activity. AEFs in response to clicks presented to the right ear were recorded with a 37-channel axial gradiometer system positioned over the left hemisphere in nine normal-hearing subjects. More than 8500 stimuli were presented in each of two independent sessions at a rate of approximately 3/s. The dipole coordinates for the dP20m derived from the two sessions typically differed by only a few millimeters. Coregistration of the dipoles with structural magnetic resonance images suggests that dP20m arises from an area close to the retroinsular origin of Heschl's gyrus. Although the dP20m is simply the point of steepest slope on the well-known middle-latency peak, P30m or Pam, it would appear that dP20m and P30m do not have the same cortical origin. Evidence is provided that P30m receives major contributions from at least two distinct cortical areas, only one of which is PAC.     

脑磁图对脑功能动态活动的定位作用

脑磁图 (magnetoencephalography, MEG)通过无创伤性的方法探测大脑生物电流所产生的磁场变化,具有很高的时间分辨率及空间分辨率,可以与 MRI结合形成磁源性影像( MSI),对脑重要功能区及癫痫灶进行精确定位,用以指导临床医师确定手术方案及指导伽玛刀治疗,以最大范围地切除病变并保留脑的重要功能区,提高患者术后生活质量;可以对轻度脑损伤患者、一过性脑缺血发作患者的脑功能损害提供客观依据.     

瘤原性佝偻病致病肿瘤的影像定位诊断

目的探讨各种影像学方法对瘤原性佝偻病致病肿瘤的定位诊断价值。方法回顾性分析13例瘤原性佝偻病的临床资料及相关影像学检查结果,与手术及病理结果对照。结果肿瘤均为单发,大小1~7cm;骨组织来源肿瘤9例,软组织来源肿瘤4例。多种影像学检查的联合应用发现和准确定位所有致病肿瘤。11例行奥曲肽显像,所有肿瘤均定位正确;在接受超声检查的8个肿瘤中,定位正确6个,另2个未显示;接受MRI(n=5)和CT检查(n=6)的肿瘤均定位正确。通过超声导向注射染料定位成功地帮助手术切除3个小肿瘤。结论多种影像学方法的综合应用对本病的临床诊治具有重要价值。     

Genetic disorders causing abnormal LDL-cholesterol levels

Various epidemiological studies and lipid intervention trials have revealed that serum LDL-cholesterol level correlates to the incidence in ischemic heart disease, and decreasing the level can prevent cardiac events. Inherited diseases causing abnormal LDL-cholesterol levels are discussed in this article, including their animal models. Familial hypercholesterolemia, familial ligand-defective apolipoprotein B100, familial combined hyperlipidemia and cholesterol ester storage disease result in elevation of serum LDL-cholesterol. On the other hand, serum LDL-cholesterol is decreased in abetalipoproteinemia and familial hypobetalipoproteinemia. The development of genetic engineering technology has elucidated the mechanism of these genetic disorders and elaborated their animal models. Although most of them cause atherosclerotic or psychoneurological diseases, fundamental therapy remains to be established, such as gene therapy.     

Towards source volume estimation of interictal spikes in focal epilepsy using magnetoencephalography

Interictal spikes are a hallmark of cortical epileptogenicity; their spatial distribution in the cortex defines the so-called ‘irritative’ zone or spiking volume (SV). Delineating the SV precisely is a challenge during the presurgical evaluation of patients with epilepsy. Magnetoencephalography (MEG) recordings enable determination of the brain sources of epileptic spikes using source localization procedures. Most previous clinical MEG studies have relied on dipole modeling of epileptic spikes, which does not permit a volumetric estimation of the spiking cortex.In the present study, we propose a new source modeling procedure, Volumetric Imaging of Epileptic Spikes (VIES). In VIES, the SV is identified as the 3D region where sources of the high frequency activities (> 20 Hz) associated with epileptic spikes are distributed. We localized these sources using a beamforming approach (DICS, Dynamic Imaging of Coherent Neural Sources). To determine the optimal parameters and accuracy of the method, we compared the SV obtained by VIES with the SV defined by the invasive gold standard, intracranial stereotactic EEG recordings (SEEG), in 21 patients with focal epilepsy. Using rigorous validation criteria based on the exact anatomical location of SEEG contacts, we found that the overall sensitivity of VIES for detecting spiking SEEG contacts was 76% and its specificity for correctly identifying non-spiking SEEG contacts was 67%, indicating a good agreement between VIES and SEEG. Moreover, we found that classical dipole clustering was not informative in 9/21 patients, while VIES enable to delineate the SV in all patients. For the 12 patients having a SV delineated both with VIES and dipole clustering, VIES method had higher sensitivity and lower specificity. This proof-of-concept study shows that VIES is a promising approach to non-invasive estimation of the SV in focal epilepsy.     

间期痫样发放对内侧颞叶癫痫脑网络的影响

目的探讨间期痫样发放对内侧颞叶癫痫患者脑静息态网络的影响,揭示间期癫痫活动发放对全脑功能的损害机制。材料与方法从45例行同步脑电f MRI数据采集单侧颞叶癫痫患者中,挑选35例(左侧颞叶癫痫患者18例、右侧颞叶癫痫患者17例),以同步脑电图监测,每一患者均采集间期痫样发放及无痫样发放状态静息态f MRI数据。采用独立成分分析方法,分别提取患者两种状态的核心网络、背侧注意网络、执行控制网络、默认网络及感觉运动网络等7套内在连接网络。采用配对t检验比较痫样发放及无痫样发放状态m TLE患者脑内在连接网络的差异。结果相比未发放状态,发放状态下颞叶癫痫患者核心网络的前扣带回功能连接增强,听觉网络的脑岛及颞上回功能连接减低。此外,背侧注意网络的顶上小叶在左侧颞叶癫痫患者表现为功能连接增强,而在右侧表现为连接减弱。前默认网络的额中回在右侧表现为功能连接减弱,而后默认网络颞中回及后扣带回在右侧表现为功能连接增强。执行控制网络的中扣带回和视觉网络枕叶皮层在左侧表现为功能连接增强。相关分析结果显示,左侧组视觉网络及右侧组听觉网络内连接强度的变化与发放状态下IEDs发放次数呈正相关。结论内侧颞叶癫痫发作间期痫样发放对脑高级认知网络及感知觉网络均产生了广泛影响,尤其是对参与脑高级认知功能网络的损害,这有助于进一步了解海马硬化这一特异性内侧颞叶癫痫在发作间期脑功能受损机制。     

难治性癫痫的致痫灶定位方法

癫痫患者中约20%~30%为难治性癫痫,手术是控制发作最有效的方法,常常可以改善患者的认知功能、行为学能力和生命质量。手术治疗的关键因素之一是准确定位致痫灶。目前有多种术前评估方法,这些方法分别从临床、神经电生理、影像学角度等提供致痫灶定位信息。目前定位致痫灶的金标准是颅内电极脑电图。建立多模式检测体系,最大程度综合各评估方法的优势,可提高致痫灶定位的准确性。近红外线波谱技术在癫痫中的应用以及致痫灶的生物标志物的研究将不断深入。     

Transient abnormal myelopoiesis (TAM) causing multiple organ failure

OBJECTIVE: To review all neonates admitted to our intensive care unit (ICU) with Transient Abnormal Myelopoiesis (TAM) - a self-limiting congenital myeloproliferative disorder seen in association with Down's syndrome. We have become concerned that in neonates requiring intensive care, TAM may not be self-limiting in its course resulting in a poor prognosis. METHOD: A retrospective review of neonates admitted to our intensive care unit (ICU) with TAM and trisomy 21 between 1996 and 2000. Clinical presentation, disease progression and laboratory findings were recorded to identify any prognostic features. RESULTS: Four cases of TAM and trisomy 21 were admitted. All four presented within the 1st week of life in respiratory failure secondary to pulmonary hypertension. All were hydropic and showed evidence of hyperviscosity. Median white cell count at presentation was 282, range 56-471 x 10(9)/l. All excepting one were treated with exchange transfusion and low dose cytarabine. Three died of multi-organ failure in spite of aggressive treatment. Post mortem examination of the infants confirmed the diagnoses and showed multiple thrombo-emboli in the lungs and livers. CONCLUSION: In infants with TAM requiring ICU, the severity of illness produced by this 'self-limiting' disease is striking and the resultant morbidity and mortality has not been reported previously. The markers for fatal outcome versus spontaneous resolution of TAM are not clear. In a dysmorphic, hydropic neonate with a high white cell count TAM should be suspected and early, aggressive exchange transfusion and simultaneous chemotherapy should be started.     

Correspondence between EEG-fMRI and EEG dipole localisation of interictal discharges in focal epilepsy

EEG-fMRI and EEG dipole source localisation are two non-invasive imaging methods that can be applied to the study of the haemodynamic and electrical consequences of epileptic discharges. Using them in combination has the potential to allow imaging with the spatial resolution of fMRI and the temporal resolution of EEG. However, although considerable data are available concerning their concordance in studies involving event-related potentials (ERPs), less is known about how well they agree in epilepsy. To this end, 17 patients were selected from a database of 57 who had undergone an EEG-fMRI scanning session followed by a separate EEG session outside of the scanner. Spatiotemporal dipole modelling was compared with the peak and closest EEG-fMRI activations and deactivations. On average, the dipoles were 58.5 mm from the voxel with the highest positive t value and 32.5 mm from the nearest activated voxel. For deactivations, the corresponding values were 60.8 and 34.0 mm. These values are considerably higher than is generally observed with ERPs, probably as a result of the relatively widespread field, which can lead to artificially deep dipoles, and the occurrence of EEG-fMRI responses remote from the presumed focus of the epileptic activity. The results suggest that EEG and MEG inverse solutions for equivalent current dipole approaches should not be strongly constrained by EEG-fMRI results in epilepsy, and that the use of distributed source modelling will be a more appropriate way of combining EEG-fMRI results with source localisation techniques.     

脑磁图联合视频脑电图定位治疗难治性癫痫病人的围术期护理

根据流行病学统计,我国癫痫发病率为0.5%～1.0%,其中20%～30%通过正规抗癫痫药物治疗2年以上不能控制临床发作症状者,发展成为难治性癫痫,需进行外科手术治疗.影响手术疗效的关键在于致痫灶的准确定位[1].     

A GABAA receptor mutation causing generalized epilepsy reduces benzodiazepine receptor binding

Understanding the consequences of newly discovered single gene mutations causing human epilepsy has the potential to yield new insights into the underlying mechanisms of this disorder. A mutation of the gamma2 subunit of the GABA(A) receptor, which substitutes glutamine for arginine at position 43 (R43Q) has been found in a familial generalized epilepsy. We tested the hypothesis that individuals affected by the GABRG2(R43Q) mutation have reduced binding to the GABA(A) receptor complex using positron emission tomography (PET) and the benzodiazepine receptor ligand [(11)C]-flumazenil. Fourteen subjects with the GABRG2(R43Q) mutation and 20 controls were studied. Benzodiazepine receptor binding was reduced in subjects with the mutation (mean whole brain binding potential for [(11)C]-flumazenil: GABA(A) mutation 0.66+/-0.1; controls 0.89+/-0.1; P<0.003). The greatest change in benzodiazepine binding occurred anteriorly, with peak differences in insular and anterior cingulate cortices revealed by statistical parametric mapping. Our findings provide in vivo evidence of reduced benzodiazepine receptor binding in subjects with the mutation. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, these findings are likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.     

Denver shunt causing abnormal right atrial mass: noninvasive determination of shunt patency by color-coded Doppler shuntography.

An unusual floating mass was detected in the right atrium of a 71-year-old man with liver cirrhosis and intractable ascites using two-dimensional echocardiography. The mass was caused by the venous tip of a Denver peritoneovenous shunt. Shunt patency could be assessed easily by compression of the pump body; this maneuver resulted in a laminar or turbulent flow that was recorded at the tip of the shunt in the right atrium by color-coded Doppler echocardiography. We are reporting the first case demonstrating the value of echocardiography in diagnosing a Denver shunt in the heart and shunt patency by color-coded Doppler shuntography.     

癫痫患者脑PET异常、MRI正常的分析

目的再认识原发性癫痫病灶脑18F-FDGPET异常、MRI正常图像。方法仪器为GE Discovery LS PET/CT和Philips1.5T磁共振。选取PET提示代谢异常而MRI显示正常的癫痫患者共87例,男60例,女27例,平均年龄20岁。结果87例PET提示18F-FDG代谢异常在MRI相应区域出现脑沟裂轻度增宽者39例,占44.8%。39例均为FDG低代谢,其中5例注射显像剂前一小时癫痫发作。结论原发性癫痫PET出现低代谢改变者已有44.8%的患者在MRI图像上存在肉眼可见的局部脑沟裂轻度增宽表现,这一病理基础也可能是导致癫痫发作期仍表现为低代谢的原因。     

Source cancellation profiles of electroencephalography and magnetoencephalography

Recorded electric potentials and magnetic fields due to cortical electrical activity have spatial spread even if their underlying brain sources are focal. Consequently, as a result of source cancellation, loss in signal amplitude and reduction in the effective signal-to-noise ratio can be expected when distributed sources are active simultaneously. Here we investigate the cancellation effects of EEG and MEG through the use of an anatomically correct forward model based on structural MRI acquired from 7 healthy adults. A boundary element model (BEM) with four compartments (brain, cerebrospinal fluid, skull and scalp) and highly accurate cortical meshes (~ 300,000 vertices) were generated. Distributed source activations were simulated using contiguous patches of active dipoles. To investigate cancellation effects in both EEG and MEG, quantitative indices were defined (source enhancement, cortical orientation disparity) and computed for varying values of the patch radius as well as for automatically parcellated gyri and sulci. Results were calculated for each cortical location, averaged over all subjects using a probabilistic atlas, and quantitatively compared between MEG and EEG. As expected, MEG sensors were found to be maximally sensitive to signals due to sources tangential to the scalp, and minimally sensitive to radial sources. Compared to EEG, however, MEG was found to be much more sensitive to signals generated antero-medially, notably in the anterior cingulate gyrus. Given that sources of activation cancel each other according to the orientation disparity of the cortex, this study provides useful methods and results for quantifying the effect of source orientation disparity upon source cancellation.     

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.     

Verification of fetal brain responses by coregistration of fetal ultrasound and fetal magnetoencephalography data

Fetal magnetoencephalography (fMEG) is used to study neurological functions of the developing fetus by measuring magnetic signals generated by electrical sources within the fetal brain. For this aim either auditory or visual stimuli are presented and evoked brain activity or spontaneous activity is measured at the sensor level. However a limiting factor of this approach is the low signal to noise ratio (SNR) of recorded signals. To overcome this limitation, advanced signal processing techniques such as spatial filters (e.g., beamformer) can be used to increase SNR. One crucial aspect of this technique is the forward model and, in general, a simple spherical head model is used. This head model is an integral part of a model search approach to analyze the data due to the lack of exact knowledge about the location of the fetal head. In the present report we overcome this limitation by a coregistration of volumetric ultrasound images with fMEG data. In a first step we validated the ultrasound to fMEG coregistration with a phantom and were able to show that the coregistration error is below 2 cm. In the second step we compared the results gained by the model search approach to the exact location of the fetal head determined on pregnant mothers by ultrasound. The results of this study clearly show that the results of the model search approach are in accordance with the location of the fetal head.     

额叶p-mTOR异常表达与外伤性癫痫发生的相关研究

目的:探索外伤性癫痫(Posttraumatic epilepsy,PTE)发生与额叶p-mTOR异常表达的相关性。方法:将78只成年雄性SD大鼠分为正常对照组(A组)6只,生理盐水对照组(B组)和癫痫模型组(C组)各36只,C组右侧额叶注射FeCl_2造模。应用免疫组化技术检测造模后1h、24h、1周、2周、4周各组大鼠额叶皮质中p-mTOR(Ser2448)的动态表达。结果:A组额叶p-mTOR(Ser2448)表达的免疫组织化学染色,神经元胞质呈浅棕色,提示弱阳性表达;B组细胞染色程度较A组加深,p-mTOR(Ser2448)表达阳性细胞数增加;C组可见细胞结构紊乱,胞质呈明显的棕黄色,提示该蛋白在细胞质中呈强阳性表达。C组和B组比较,1h表达开始升高(t=-1.435,P=0.182),但差异无统计学意义,1周表达高峰(t=-4.073,P=0.002),2周降低(t=-2.614,P=0.026),4周时再次升高(t=-2.506,P=0.031),差异具有统计学意义(均P0.05)。结论:PTE的发病机制可能与mTOR信号通路上pmTOR(Ser2448)的表达异常增加有关。