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．     

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．     

基于内在功能连接推定抑郁症脑网络效率的改变

本文研究了在保留最大化内在功能连接条件下抑郁症患者脑网络效率的改变,并探索了改变的拓扑效率和抑郁症病理学之间的关系.为此,我们收集了20例抑郁症患者和20例在年龄、性别和教育水平相匹配的健康被试的静息态功能磁共振图像数据.图论分析显示,与健康对照组比较,抑郁症患者的节点效率减少在左海马旁回、右杏仁核,左颞横回和左颞极(颞中回)减少.减少的节点效率表明,在抑郁症患者脑网络中这些区域传送信息到其他区域的能力减弱.此外,发现局部效率降低在左内侧额上回、左眶部额上回、右回直肌、左杏仁核、右顶上回、左丘脑和左颞极(颞中回).并且发现左内侧额上回、左杏仁核、左丘脑与PHQ-9得分呈负相关.降低的局部效率表明抑郁症患者脑网络中这些区域的局部网络信息传送能力受到抑制.这些结果进一步确认在抑郁症患者中涉及情感信息处理的前额-丘脑-边缘区域被破坏.我们的发现为抑郁症病人的辅助诊断提供了新的潜在生物学标记物.     

偏头痛患者体感刺激下脑电信号的功能连接（英文）

目的 偏头痛是一种复杂的脑功能障碍性疾病,全球范围内患病率为14.4%。功能连接测量两个神经信号之间的统计学相互依赖性,不同的功能连接反映了大脑区域协同工作的不同模式。因此,研究不同脑区的功能连接对于理解偏头痛的病理生理机制具有十分重要的意义。以往基于脑电图对偏头痛患者脑功能连接的分析主要集中在视觉和疼痛刺激。本文尝试研究偏头痛患者在发作间期对体感刺激的皮质反应,以进一步了解偏头痛的神经功能障碍,为偏头痛的预防和治疗提供线索。方法 招募23例无先兆偏头痛患者,10例有先兆偏头痛患者,28名健康对照者。所有受试者均进行详细的基本资料和病史采集,完善量表评估,在正中神经体感刺激下进行脑电图记录。计算68个脑区的相干性作为功能连接,并评估功能连接与临床参数的相关性。结果 在正中神经体感刺激下,无先兆偏头痛和有先兆偏头痛患者的脑电功能连接与对照组相比存在差异,异常的脑电功能连接主要位于感觉辨别、疼痛调节、情绪认知和视觉处理等区域。无先兆偏头痛和有先兆偏头痛患者的大脑皮层对体感刺激可能具有相同的反应方式。偏头痛患者的功能连接异常与临床特征之间存在相关性,可以部分反映偏头痛的严重程度。结论 本研究...     

基于脑功能连接网络离心率的轻微肝性脑病研究

全脑功能连接显示轻微肝性脑病(minimal hepatic encephalopathy,MHE)患者的皮层-基底节-丘脑环路受损,但无法量化该改变。通过对比MHE患者组和健康组的全脑功能连接网络的全局指标,发现MHE患者具有更大的图连接指数、图直径、图半径和直径指数,支持这些指标在MHE疾病的全脑功能连接水平上的有效性和可靠性。图连接指数、图直径及直径指数与数字符号实验指标相关,直径指数与数字连接实验指标相关,反映MHE患者的脑功能改变。离心率和离心率连接指数显示MHE患者大部分脑区指向基底节区域,支持MHE患者的脑区连接通路、特别是连接基底节区域的通路很可能出现阻滞甚至断裂。     

带状疱疹后遗神经痛患者脑基础活动改变的功能核磁共振研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是临床上一种慢性顽固性神经病理性疼痛,然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨带状疱疹后遗神经痛患者的相关脑区活动,利用功能核磁共振成像低频振幅振荡(ALFF)技术观察带状疱疹后遗神经痛患者的基础脑区活动.8名带状疱疹后遗神经痛患者与8名性别、年龄相匹配的健康者行静息态功能磁共振(f MRI)成像扫描,用SPM8中的多重回归分析,在控制被试年龄、性别、教育年限的影响下,将每个体素的ALFF值同每个被试的病程、视觉模拟评分(visual analog scale,VAS)进行相关分析.与健康志愿者相比,PHN组与VAS评分相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA11/46/47)、右侧顶叶(BA40)、右侧舌回(BA17/18/19);与VAS评分相关的ALFF值降低的脑区有:右侧颞中回(BA21)、左侧舌回(BA17/18)、右侧小脑前叶、左侧后扣带回(BA30/19)和右侧中央前回(BA3/4/6);PHN组与病程相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA9/10/11/47)、左侧颞上回(BA38)、右侧顶叶和右侧舌回(BA17/18/19);与病程相关ALFF值降低的脑区有:左侧海马旁回(BA28)、右侧小脑前叶、左侧扣带回(BA24)、右侧颞上回(BA13)、左侧中央前回和右侧顶下小叶(BA39/40).研究结果提示,涉及疼痛的情绪、警觉行为、注意的脑区在带状疱疹后遗痛慢性疼痛的产生和维持中发挥重要作用.     

语言控制和一般领域认知控制的脑机制的重合和分离

双语者能根据不同的场合和交流对象选择目标语言进行交流.已有的研究发现,双语者需要通过抑制控制选择合适的语言.本研究使用功能性核磁共振(f MRI)技术,扫描22名汉-英双语者完成语言切换任务和西蒙切换任务时的脑活动状况,通过联合分析和分离分析的方法,揭示了双语产生过程中语言控制与一般领域的认知控制的脑机制的重合与分离.结果发现,双语产生过程中,语言控制需要使用一般领域的施加抑制和解除抑制机制.其中,语言控制与施加抑制共同涉及了额上回、前辅助运动区/背侧前扣带回、壳核和右侧顶上小叶的活动;语言控制与解除抑制都需要左侧顶上小叶的参与.此外发现,双语控制相比于一般领域的控制,需要特异性地激活左侧中央后回、左侧颞上回、左侧楔前叶、中后部扣带回、后辅助运动区、右侧颞中回、右侧舌回、右侧缘上回和双侧小脑等脑区,以发挥与发音动作、词汇提取、语义记忆有关的认知控制功能.这表明,语言控制与一般领域的认知控制既存在重合的脑机制,也存在分离的脑机制.     

基于fMRI的脑功能整合数据分析方法综述

脑功能成像在人脑信息处理和认知活动的神经关联中发挥了不可轻视的作用.从大脑功能整合出发,可以将脑功能成像数据分析方法分为探测大脑功能整合的功能连接和有效连接两方面,功能连接探究空间远离的两个脑区之间的连接,有效连接研究一个脑区对另一个脑区作用的大小.根据这两个概念,相应地可以将功能磁共振数据分析方法分为两大类.本文着重...     

基于内在功能连接推定抑郁症脑网络效率的改变（英文）

本文研究了在保留最大化内在功能连接条件下抑郁症患者脑网络效率的改变,并探索了改变的拓扑效率和抑郁症病理学之间的关系.为此,我们收集了20例抑郁症患者和20例在年龄、性别和教育水平相匹配的健康被试的静息态功能磁共振图像数据.图论分析显示,与健康对照组比较,抑郁症患者的节点效率减少在左海马旁回、右杏仁核,左颞横回和左颞极(颞中回)减少.减少的节点效率表明,在抑郁症患者脑网络中这些区域传送信息到其他区域的能力减弱.此外,发现局部效率降低在左内侧额上回、左眶部额上回、右回直肌、左杏仁核、右顶上回、左丘脑和左颞极(颞中回).并且发现左内侧额上回、左杏仁核、左丘脑与PHQ-9得分呈负相关.降低的局部效率表明抑郁症患者脑网络中这些区域的局部网络信息传送能力受到抑制.这些结果进一步确认在抑郁症患者中涉及情感信息处理的前额-丘脑-边缘区域被破坏.我们的发现为抑郁症病人的辅助诊断提供了新的潜在生物学标记物.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Brain evolution and development: adaptation,allometry and constraint

Phenotypic traits are products of two processes: evolution and development. But how do these processes combine to produce integrated phenotypes? Comparative studies identify consistent patterns of covariation, or allometries, between brain and body size, and between brain components, indicating the presence of significant constraints limiting independent evolution of separate parts. These constraints are poorly understood, but in principle could be either developmental or functional. The developmental constraints hypothesis suggests that individual components (brain and body size, or individual brain components) tend to evolve together because natural selection operates on relatively simple developmental mechanisms that affect the growth of all parts in a concerted manner. The functional constraints hypothesis suggests that correlated change reflects the action of selection on distributed functional systems connecting the different sub-components, predicting more complex patterns of mosaic change at the level of the functional systems and more complex genetic and developmental mechanisms. These hypotheses are not mutually exclusive but make different predictions. We review recent genetic and neurodevelopmental evidence, concluding that functional rather than developmental constraints are the main cause of the observed patterns.     

A Common Left Occipito-Temporal Dysfunction in Developmental Dyslexia and Acquired Letter-By-Letter Reading?

Background

We used fMRI to examine functional brain abnormalities of German-speaking dyslexics who suffer from slow effortful reading but not from a reading accuracy problem. Similar to acquired cases of letter-by-letter reading, the developmental cases exhibited an abnormal strong effect of length (i.e., number of letters) on response time for words and pseudowords.

Results

Corresponding to lesions of left occipito-temporal (OT) regions in acquired cases, we found a dysfunction of this region in our developmental cases who failed to exhibit responsiveness of left OT regions to the length of words and pseudowords. This abnormality in the left OT cortex was accompanied by absent responsiveness to increased sublexical reading demands in phonological inferior frontal gyrus (IFG) regions. Interestingly, there was no abnormality in the left superior temporal cortex which—corresponding to the onological deficit explanation—is considered to be the prime locus of the reading difficulties of developmental dyslexia cases.

Conclusions

The present functional imaging results suggest that developmental dyslexia similar to acquired letter-by-letter reading is due to a primary dysfunction of left OT regions.     

The Nature and Composition of the Internal Environment of the Developing Brain

1. The fetal brain develops within its own environment, which is protected from free exchange of most molecules among its extracellular fluid, blood plasma, and cerebrospinal fluid (CSF) by a set of mechanisms described collectively as brain barriers.2. There are high concentrations of proteins in fetal CSF, which are due not to immaturity of the blood–CSF barrier (tight junctions between the epithelial cells of the choroid plexus), but to a specialized transcellular mechanism that specifically transfers some proteins across choroid plexus epithelial cells in the immature brain.3. The proteins in CSF are excluded from the extracellular fluid of the immature brain by the presence of barriers at the CSF–brain interfaces on the inner and outer surfaces of the immature brain. These barriers are not present in the adult.4. Some plasma proteins are present within the cells of the developing brain. Their presence may be explained by a combination of specific uptake from the CSF and synthesis in situ. 5. Information about the composition of the CSF (electrolytes as well as proteins) in the developing brain is of importance for the culture conditions used for experiments with fetal brain tissue in vitro, as neurons in the developing brain are exposed to relatively high concentrations of proteins only when they have cell surface membrane contact with CSF.6. The developmental importance of high protein concentrations in CSF of the immature brain is not understood but may be involved in providing the physical force (colloid osmotic pressure) for expansion of the cerebral ventricles during brain development, as well as possibly having nutritive and specific cell development functions.     

The unfolding story of two lissencephaly genes and brain development

Formation of our highly structured human brain involves a cascade of events, including differentiation, fate determination, and migration of neural precursors. In humans, unlike many other organisms, the cerebral cortex is the largest component of the brain. As in other mammals, the human cerebral cortex is located on the surface of the telencephalon and generally consists of six layers that are formed in an orderly fashion. During neuronal development, newly born neurons, moving in a radial direction, must migrate through previously formed layers to reach their proper cortical position. This is one of several neuronal migration routes that takes place in the developing brain; other modes of migration are tangential. Abnormal neuronal migration may in turn result in abnormal development of the cortical layers and deleterious consequences, such as Lissencephaly. Lissencephaly, a severe brain malformation, can be caused by mutations in one of two known genes:LIS1 anddoublecortin (DCX). Recent in vitro and in vivo studies, report on possible functions for these gene products.     

Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees

Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss‐of‐function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non‐synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1‐weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.     

Mechanism Interpretation of the Biological Brain Cooling and Its Inspiration on Bionic Engineering

The brain is one of the most important organs in a biological body which can only work in a relatively stable temperature range. However, many environmental factors in biosphere would cause cerebral temperature fluctuations. To sustain and regulate the brain temperature, many mechanisms of biological brain cooling have been evolved, including Selective Brain Cooling (SBC), cooling through surface water evaporation, respiration, behavior response and using special anatomical appendages. This article is dedicated to present a summarization and systematic interpretation on brain cooling strategies developed in animals by classifying and comparatively analyzing each typical biological brain cooling mechanism from the perspective of bio-heat transfer. Meanwhile, inspirations from such cooling in nature were proposed for developing advanced bionic engineering technologies especially with two focuses on therapeutic hypothermia and computer chip cooling areas. It is expected that many innovations can be achieved along this way to find out new cooling methodologies for a wide variety of industrial applications which will be highly efficient, energy saving, flexible or even intelligent.     

Barriers in the Immature Brain

1. The term blood–brain barrier describes a range of mechanisms that control the exchange of molecules between the internal environment of the brain and the rest of the body.2. The underlying morphological feature of these barriers is the presence of tight junctions which are present between cerebral endothelial cells and between choroid plexus epithelial cells. These junctions are present in blood vessels in fetal brain and are effective in restricting entry of proteins from blood into brain and cerebrospinal fluid. However, some features of the junctions appear to mature during brain development.3. Although proteins do not penetrate into the extracellular space of the immature brain, they do penetrate into cerebrospinal fluid by a mechanism that is considered in the accompanying review (Dziegielewska et al., 2000).4. In the immature brain there are additional morphological barriers at the interface between cerebrospinal fluid and brain tissue: strap junctions at the inner neuroependymal surface and these and other intercellular membrane specializations at the outer (pia–arachnoid) surface. These barriers disappear later in development and are absent in the adult.5. There is a decline in permeability to low molecular weight lipid-insoluble compounds during brain development which appears to be due mainly to a decrease in the intrinsic permeability of the blood–brain and blood–cerebrospinal fluid interfaces.     

Brain functional network modeling and analysis based on fMRI: a systematic review

In recent years, the number of patients with neurodegenerative diseases (i.e., Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment) and mental disorders (i.e., depression, anxiety and schizophrenia) have increased dramatically. Researchers have found that complex network analysis can reveal the topology of brain functional networks, such as small-world, scale-free, etc. In the study of brain diseases, it has been found that these topologies have undergoed abnormal changes in different degrees. Therefore, the research of brain functional networks can not only provide a new perspective for understanding the pathological mechanism of neurological and psychiatric diseases, but also provide assistance for the early diagnosis. Focusing on the study of human brain functional networks, this paper reviews the research results in recent years. First, this paper introduces the background of the study of brain functional networks under complex network theory and the important role of topological properties in the study of brain diseases. Second, the paper describes how to construct a brain functional network using neural image data. Third, the common methods of functional network analysis, including network structure analysis and disease classification, are introduced. Fourth, the role of brain functional networks in pathological study, analysis and diagnosis of brain functional diseases is studied. Finally, the paper summarizes the existing studies of brain functional networks and points out the problems and future research directions.     

血脑屏障与脑血管疾病的相关研究

血脑屏障（blood brain barrier,BBB）的主要结构包括：脑毛细血管内皮细胞及其间的紧密连接（tight junction,TJ）、基底膜、基 底膜下星型胶质细胞终足。血脑屏障是存在于血液和脑组织之间的一层屏障系统,在许多大脑疾患的病理过程中,BBB 的破坏导 致通透性增高都是不可避免的一个环节。BBB是保证中枢神经系统的正常生理功能的重要屏障系统。目前已有大量关于血脑屏 障通透性在脑血管疾病中的变化研究。本文分别从血脑屏障的结构和功能,药物通过血脑屏障的方法和功能,脑缺血损伤、阿尔 茨海默病、帕金森病和多发性硬化症等不同的脑病变与血脑屏障通透性的变化及中医药应用等方面做一综述。有针对性地对 BBB和大脑疾病进行进一步的研究与探索,将会为临床治疗相关疾病带来新的视角与机遇。     

Glycosyltransferases in Different Brain Regions During Chick Embryo Development

Glycosphingolipids, in particular gangliosides, play a crucial role in neuronal development and are known to change dramatically in total content and distribution in different brain areas during embryogenesis. In the present work we analyzed the activity of enzymes involved in the metabolism of gangliosides, at different periods of functional maturation in different regions of chick embryo brain. Our data demonstrate differences in the enzymatic activities in the examined areas; these differences might be correlated with the functional lateralization occurring in the brain during development. Significative differences were found in glycosphingolipid composition between controlateral cerebral hemispheres and optic lobes; these results together with previous data we found, contribute to reinforce our hypothesis on the occurrence of biochemical lateralization during early brain development.