神经信息学的原理与展望

神经信息学是研究神经系统信息的载体形式,神经信息的产生、传输、加工、编码、存储与提取机理,以及建立神经数据库系统的科学。它是脑科学,信息科学和计算机科学相互交叉的边缘学科。神经信息学可分为分子神经信息学和系统神经信息学两个层次。神经信息编码可分为神经元脉冲序列的数字编码和突触联结权重编码两种编码方式。对21世纪神经信息学可能取得的新进展进行分析和预测,并论证开展人类神经组计划（HuNP）和建立神经数据库系统的必要性与可行性。对人类神经计划与人类脑计划的异同步,进行比较和讨论。     

神经营养素脑内功能及其表达调节

神经营养素（neurotrophin,NT）是与神经生长因子同源的一类神经营养因子,它们在神经系统的分化和发育过程中起着重要作用,并具有治疗某些脑疾病的潜在应用价值．文章较全面地阐述了NT在脑内既相互交叉又有各自特性的生理功能,并系统地介绍了脑内NT表达调节方面的研究进展．     

正常人长时数字记忆信息提取的神经基础的功能磁共振研究

本文旨在通过功能磁共振成像(functional magnetic resonance imaging,fMRI)技术研究正常人进行长时数字记忆信息提取的神经基础。选取22名右利手志愿者进行长时数字记忆任务实验,采用组块设计,记忆任务与对照任务交替进行,同时利用Siemens 1.5T超导型磁共振仪进行fMRI成像,采用SPM99软件进行数据分析,脑功能区定位在Talairach坐标中显示。结果显示被试者在进行长时数字记忆提取任务时,激活最显著的皮层是左侧额中回(Brodmann分区9区,BA9区),另外左额叶内侧回、左额下回、右额下回、扣带回、左顶下小叶、左顶上小叶、右顶上小叶、右颞中回、左枕舌回、左枕中回、右中脑、小脑、右尾状核尾部等结构也有激活,各大脑皮层的激活均呈现明显的左侧半球优势。根据上述结果推论,长时数字记忆由以左侧大脑半球为优势的各脑区共同参与完成,其中左侧额叶外侧面可能是信息提取的重要结构,而其它脑叶及其之间的广泛联系可能在数字信息的加工、处理和存储中起重要作用。     

综述:阿尔茨海默病的神经影像学研究进展

阿尔茨海默病(Alzheimer's disease,AD)是以记忆和其他高级认知功能下降为特征的神经退行性疾病．早期的神经影像学研究通常是探索AD患者局部脑区的结构和功能变化．随着多模态神经影像技术和人脑连接组学研究方法的发展,研究者已经能够考察AD患者脑结构和功能连接通路．采用这些方法,最近的研究已经发现,AD患者脑网络的连接强度、网络效率、模块化组织和核心脑区连接的下降,并发现这些变化与患者的记忆评分等密切相关．这些新方法和新技术的出现不仅提供了新颖的观点来解释AD病的脑区失连接病理生理机制,而且发现的AD异常脑连接模式可能作为敏感特征应用于AD早期辅助诊断的影像标记物研究．特别重要的是,研究表明,在AD患者脑神经网络出现的异常连接模式,在AD前期即轻度认知障碍期患者中也已出现,表明了将AD影像学研究的重点前移到AD前期这一可治疗阶段的重要性和迫切性．     

功能区胶质瘤患者初级运动皮层激活的偏侧化及运动网络功能连接研究

无运动障碍的功能区胶质瘤患者,其手术风险较高,结合手运动任务态功能磁共振(fMRI)及运动网络功能连接能否更准确的评估手术风险需要进一步探索.本研究收集24例运动功能区胶质瘤且无明显肢体运动功能障碍的患者,非运动功能区胶质瘤患者8例,术前进行fMRI手运动任务态及静息态检查,术后3个月对患者进行随访.计算初级运动皮质(M1)激活的偏侧化指数(lateralization indices,LI).选取运动网络感兴趣区域(ROI),计算双侧M1与各ROI间功能连接系数(FC).运用受试者工作特性曲线(receiver operating characteristic curve,ROC)评估M1激活的LI对术后偏瘫的预测效能.同非运动功能区胶质瘤患者相比,运动功能区胶质瘤患者M1激活LI显著升高(P=0.001).同术后未偏瘫功能区胶质瘤患者相比,术后偏瘫患者M1激活LI值显著升高(P=0.011).ROC曲线下面积(AUC)=0.867,临界点LI=0.31,LI≥0.31对术后偏瘫预测灵敏性为87.5%,特异性为87.5%.以M1激活LI≥0.31将病人分为手术高风险组及低风险组,手术高风险组患者双侧M1与运动网络多个ROI间FC出现显著改变.本研究中功能区胶质瘤患者虽无肢体运动功能障碍,但肿瘤对功能区皮层激活及运动网络FC已有不同程度的破坏;结合任务态及静息态fMRI可以更好地评估手术风险并了解机体功能受损及代偿机制.     

内源性神经干细胞与脑老化的治疗

近十几年研究发现成年人脑神经元可以再生,使人们重新认识老年脑神经细胞的可塑性,它为脑损伤的修复带来新的希望。最新研究表明,神经再生可被调控,是一种新的修复机制。这使得利用内源性神经干细胞治疗老龄相关的神经退行性疾病成为可能。     

孤独症谱系障碍的遗传基础与神经机制

孤独症谱系障碍(autism spectrum disorder,ASD)是一种神经精神障碍,主要表现为社会交往障碍、交流障碍以及局限性的兴趣和重复刻板的行为模式三个主要核心症状．本文介绍了ASD的遗传基础和神经机制的最新研究进展．ASD具有较高的遗传率,且ASD个体的5-羟色胺和睾丸激素都较高．神经影像学研究发现,ASD个体的杏仁核、扣带回、梭状回、镜像神经元和前额叶等大脑区域在结构和功能上都与正常发育个体存在差异,但在个别区域激活模式的差异方向上仍存在不一致的地方．此外,功能连接的研究结果也证实了ASD个体连接不良的假设．未来的研究应该更多地着眼于如何利用这些基础研究成果为临床上提出有效的治疗和训练方式．     

中国科学院武汉物理与数学研究所神经影像实验室简介

中国科学院武汉物理与数学研究所神经影像实验室建立于2007年4月,由国家杰出青年基金获得者徐富强研究员领导。综合不同层次和尺度的神经生物学的方法和技术是该实验室的显著特点。现已建立分子生物学、生物化学、神经环路示踪、微透析、电生理、光学成像、磁共振成像、动物行为等方法和技术,     

人类疱疹病毒7开放读码框U41功能的初步探讨

应用免疫荧光检测U41蛋白的细胞内定位,RT-PCR检测U41RNA的表达时相,DNA结合试验检测U41蛋白对单、双链DNA的不同结合能力,对人类疱疹病毒7(human herpesvirus 7,HHV-7)U41的部分功能进行分析鉴定.免疫荧光检测显示,无论在HHV-7感染细胞或HHV-7 U41转染细胞,U41蛋白都是仅在其胞核中呈弥漫性分布.在分别加入环己酰亚胺(cycloheximide)和磷甲酸(phosphonoformic acid)作为蛋白合成和核酸合成抑制剂的感染细胞中,U41的表达时相检测结果显示,U41蛋白在HHV-7感染细胞中是一早期表达蛋白.通过DNA结合试验发现,U41蛋白能结合单链DNA而不能结合双链DNA.提示U41的主要功能是保持DNA模板的合适构型,以便DNA的延伸和病毒DNA的合成.     

神经营养因子NGF、BDNF与围绝经期妇女认知功能关系的研究进展

神经营养因子(NTFs)是近几年神经科学研究的热点,研究显示它在神经系统中发挥独特的作用,尤其是神经生长因子(NGF)、脑源性神经营养因子(BDNF)在脑内功能及其表达调控方面具有重要作用。围绝经期妇女随着雌激素水平的降低会产生认知功能的减退,有研究发现去卵巢动物(OVX)雌激素水平降低可以导致某些NGF、BDNF的丢失。通过启动内源性NGF和BDNF的表达而实现对神经元的保护可能为雌激素替代治疗(ERT)脑保护作用的一种机制。本文就近几年的研究进展做一简要综述。     

Neurodegeneration with brain iron accumulation — Clinical syndromes and neuroimaging

Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this article, we discuss seven NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are Friedreich ataxia (FA), pantothenate kinase 2-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Kufor-Rakeb disease (KRD), aceruloplasminemia, and neuroferritinopathy. An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Brain Magnetic Resonance in the Diagnostic Evaluation of Mitochondrial Encephalopathies

Brain MR imaging techniques are important ancillary tests in the diagnosis of a suspected mitochondrial encephalopathy since they provide details on brain structural and metabolic abnormalities. This is particularly true in children where non-specific neurologic symptoms are common, biochemical findings can be marginal and genetic defects may be not discovered. MR imaging modalities include conventional, or structural, imaging (MRI) and functional, or ultrastructural, imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI––ASL). Among them MRI and MRS are the main tools for diagnosis and work up of MD, and this review will focus mainly on them. The MRI findings of MD are very heterogeneous, as they depend on the metabolic brain defects, age of the patient, stage and severity of the disease. No correlation has been found between genetic defects and neuroimaging picture; however, some relationships between MR findings and clinical phenotypes may be identified. Different combinations of MRI signal abnormalities are often encountered but the most common findings may be summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii) leukodystrophic-like. Regarding the functional MR techniques, only proton MRS plays an important role in demonstrating an oxidative metabolism impairment in the brain since it can show the accumulation of lactate, present as a doublet peak at 1.33 ppm. Assessment of lactate should be always performed on brain tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS abnormalities can be of different types, and two distinct patterns can be recognized: non-specific and specific. The specific metabolic profiles, although not frequent to find, are highly pathognomonic of MD. The un-specific metabolic profiles add value to structural images in allowing to define the lesion load and to monitor the response to therapy trials.     

Cardiac magnetic resonance imaging in daily practice in a peripheral medical centre: description of the first 383 patients

Background. Cardiac magnetic resonance (CMR) imaging has evolved over the last decade into an indispensable diagnostic instrument. CMR imaging noninvasively provides structural, functional and morphological information with high spatial resolution and an unlimited field of view. Since October 2006 the VieCuri Medical Centre in Venlo has a CMR scanner at its disposal.Objectives. The goal of this study was to analyse the impact of CMR imaging on diagnosis and treatment in daily practice in the setting of a medium-volume peripheral hospital.Methods. All patients who underwent CMR imaging between October 2006 and November 2008 were included in this analysis. The medical history before and after the CMR scan, the application form for CMR imaging and the outcome of the scans were reviewed. CMR images, obtained using a 1.5-T magnetic resonance imaging system, were reviewed by a multidisciplinary team.Results. In 235 patients CMR imaging demonstrated one or more abnormalities, whereas CMR imaging did not identify any abnormalities in 148 patients. CMR imaging confirmed an expected finding in 166 cases, identified an unexpected condition in 69 cases, ruled out an expected finding in 59 cases and ruled out a suspected condition in 89 cases. Due to better insight into diagnosis, CMR imaging resulted in a change of treatment in 166 of the total of 383 CMR scans (43%).Conclusion. In a relevant number of cases CMR imaging leads to a change in the treatment of a patient, proving the value of CMR imaging as a diagnostic modality. Therefore, CMR imaging is an excellent opportunity for peripheral medical centres to improve efficiency and the standard of patient care. (Neth Heart J 2010;18:524–30.)     

缺血性脑卒中患者脑内微出血的发生及危险因素

目的:探讨脑内微出血(CMB)在缺血性脑卒中患者中的发生及相关危险因素。方法:连续选取住院的缺血性脑卒中患者250例,分析其磁共振成像(MRI)表现。根据有无CMB将患者分为CMB组(80例)及无CMB组(170例)。详细记录临床资料,观察CMB的个数、陈旧性腔隙性脑梗死的个数和脑白质改变(WMC)的严重程度。结果:单因素分析显示年龄、高血压病、既往脑梗死病史、脑白质改变、陈旧性腔隙性脑梗死及口服抗血小板聚集药物史与CMB的发生有关。Logistic回归分析显示高血压、既往有脑梗死病史及WMC分值为CMB的独立危险因素。结论:CMB与脑微血管病变之间有密切关系,高血压、既往有脑梗死病史及WMC分值为缺血性脑卒中患者发生CMB的独立危险因素。     

fMRI与DTI在神经科学研究中的联合应用

功能磁共振成像(fMRI)和扩散张量成像(DTI)是近年来磁共振成像领域出现的两种新的成像技术,它们各具特色。功能磁共振成像能对人脑相关任务激活区进行准确的功能定位并提供相关皮层区域的磁共振信号改变特征信息,但时于脑白质相关改变则不能提供任何信息;扩散张量成像则是目前能够在体呈现人脑解剖连接的唯一手段,采用它能对人脑组织,包括灰质和白质的扩散特性进行定量研究,并且能够形象显示人脑生理或病理状态下的纤维束形态、走行等,但扩散张量成像不能提供皮层功能情况信息。功能磁共振成像和扩散张量成像技术具有很强的互补性,二者联合在神经科学研究中具有广阔的应用前景。目前也正成为神经科学研究领域的热点之一。本文从功能磁共振成像和扩散张量成像的原理、特点,二者结合应用的具体方法以及目前二者在神经科学各基础及临床学科结合应用的研究进展进行了综述。     

Development and sexual dimorphism of the pituitary gland

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.     

基于fMRI观察正常人脑中枢对针刺得气感反应的初步研究

目的:运用功能性磁共振成像技术观察正常人脑中枢对针刺得气感的反应特点,探索针刺得气的物质基础。方法:按照纳入排除标准收集男、女健康志愿者各35例,随机分为2组,针刺组40人,假针刺组30人,分别以外关穴针刺与假针刺作为刺激因素。采用Block方法设计刺激程序,运用功能性磁共振成像技术收集脑中枢反应信号。扫描完毕随即使用针刺感觉量表评价受试对象的感觉,依据感觉量化结果将图像数据分为针刺得气感组与无感觉对照组,以P≤0.0001,uncorrected,K10为统计检验显著性标准,以对照无感觉组为基线,在Matlab平台上采用SPM2.0软件包对图像数据进行处理和分析。结果:(1)得气效应:针刺组29人、假针刺组1人以酸麻胀重等得气指征为主,VAS评分4.62±3.05;针刺组2人轻微刺痛感,假针刺组21人无感觉、5人轻微刺痛感。(2)脑中枢激活效应:针刺得气激活的脑功能区有双侧额上回(BA6)、额下回(BA47)、缘上回(BA40),左侧额中回(BA47)、中央前回(BA10)、颞中回(BA21),右侧额中回(BA10)、顶下小叶(BA40)、中央前回(BA6)、颞上回(BA10)、颞中回(BA39)、颞下回(BA20)。结论:针刺得气感能特异性的激活正常人脑功能区,针刺得气效应与脑中枢密切相关。     

血管性认知功能障碍的研究进展

血管性认知功能障碍(VCI)是目前严重危害老年人健康的疾病之一。随着人类寿命的延长、人口老龄化的增加,将会有越来越多的老年人患者患上VCI。对于VCI的早期、有效的干预有重要的临床意义,也受到人们的广泛关注。如能预防甚至治疗VCI的产生,可从很大程度上提高老年人的生活质量,减轻家庭和社会的负担。现就近年来对血管性认知功能障碍的相关研究予以综述。     

PEGylation of protein-based MRI contrast agents improves relaxivities and biocompatibilities

Magnetic resonance imaging (MRI) has emerged as a leading diagnostic technique in clinical and preclinical settings. However, the application of MRI to assess specific disease markers for diagnosis and monitoring drug effect has been severely hampered by the lack of desired contrast agents with high relaxivities, and optimized in vivo retention time. We have reported the development of protein-based MRI contrast agents (ProCA1) by rational design of Gd^3 + binding sites into a stable protein resulting in significantly increased longitudinal (r₁) and transverse (r₂) relaxivities compared to Gd-DTPA. Here, we report a further improvement of protein contrast agents ProCA1 for in vivo imaging by protein modification with various sizes of polyethylene glycol (PEG) chain. PEGylation results in significant increases of both r₁ and r₂ relaxivities (up to 200%), and these high relaxivities persist even at field strengths up to 9.4 T. In addition, our experimental results demonstrate that modified contrast agents have significant improvement of in vivo MR imaging and biocompatibilities including dose efficiency, protein solubility, blood retention time and decreased immunogenicity. Such improvement can be important to the animal imaging and pre-clinical research at high or ultra-high field where there is an urgent need for molecular imaging probes and optimized contrast agent.