Development of the human fetal cerebellum in the second trimester: a post mortem magnetic resonance imaging evaluation

The cerebellum is one of the most important structures in the posterior cranial fossa, but the characterization of its development by magnetic resonance imaging (MRI) is incomplete. We scanned 40 fetuses that had no morphological brain disorder at 14-22 weeks of gestation using 7.0 T MRI. Amira 4.1 software was used to determine morphological parameters of the fetal cerebellum, which included the cerebellar volume (CV), transverse cerebellar diameter (TCD), and the length and width of the vermis. The relationship between these measurements and gestational age (GA) was analysed. We found that the primary fissure was visible at week 14 of gestation. From week 16, the prepyramidal fissure, the secondary fissure and the dentate nucleus could be identified. The posterolateral fissure and the fourth ventricle were recognized at week 17, whereas the tentorium of the cerebellum was visible at week 20. The relationships between GA and CV, TCD, and the width and length of the vermis were described adequately by second-order polynomial regression curves. The ratios between TCD and vermis length and between TCD and vermis width decreased with GA. These results show that 7.0 T MRI can show the trajectory of cerebellar development clearly. They increase our understanding of normal cerebellar development in the fetus, and will facilitate the diagnosis of pathological intrauterine changes in the cerebellum.     

Diffusion tensor imaging of diffuse axonal injury in a rat brain trauma model

Diffusion tensor imaging (DTI) was used to study traumatic brain injury. The impact-acceleration trauma model was used in rats. Here, in addition to diffusivities (mean, axial and radial), fractional anisotropy (FA) was used, in particular, as a parameter to characterize the cerebral tissue early after trauma. DTI was implemented at 7 T using fast spiral k-space sampling and the twice-refocused spin echo radiofrequency sequence for eddy current minimization. The method was carefully validated on different phantom measurements. DTI of a trauma group (n = 5), as well as a sham group (n = 5), was performed at different time points during 6 h following traumatic brain injury. Two cerebral regions, the cortex and corpus callosum, were analyzed carefully. A significant decrease in diffusivity in the trauma group versus the sham group was observed, suggesting the predominance of cellular edema in both cerebral regions. No significant FA change was detected in the cortex. In the corpus callosum of the trauma group, the FA indices were significantly lower. A net discontinuity in fiber reconstructions in the corpus callosum was observed by fiber tracking using DTI. Histological analysis using Hoechst, myelin basic protein and Bielschowsky staining showed fiber disorganization in the corpus callosum in the brains of the trauma group. On the basis of our histology results and the characteristics of the impact-acceleration model responsible for the presence of diffuse axonal injury, the detection of low FA caused by a drastic reduction in axial diffusivity and the presence of fiber disconnections of the DTI track in the corpus callosum were considered to be related to the presence of diffuse axonal injury.     

A new approach for exploring functional development of fetal brain pathways

Study of functional development of central pathways in fetuses is challenging due to the lack of methods available. In this article, we present a novel approach to test if and when central functional pathways are established by a combination of mapping with c‐fos and chronically cannulated fetuses in utero. This approach is based on brain structures such as circumventricular organs (CVOs) that lack the blood–brain barrier (BBB), but are rich in sensors to peripheral signals and contain projections to other brain regions. If signaling molecules in the blood that are too large to cross the BBB induced c‐fos expression in both the CVOs and other nuclei inside the fetal brain, this can be evidence that projections from the CVOs to those nuclei are established and functional. This is a useful real‐time method to explore the status of functional maturation of pathways between the CVOs and other brain areas in developing fetuses. Notably, at the moment, this is the first and only in vivo method that can detect functional projections in the fetal brain in vitro. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 384–388, 2009.     

Sublaminar organization of the human subplate: developmental changes in the distribution of neurons,glia, growing axons and extracellular matrix

The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypoxic‐ischemic lesions, autism and schizophrenia. The main cytological features of the SP, such as low cell density, early differentiation of neurons and glia, plexiform arrangement of axons and dendrites, presence of synapses and a large amount of extracellular matrix (ECM) distinguish this compartment from the cell‐dense cortical plate (CP; towards pia) and large fiber bundles of external axonal strata of fetal white matter (towards ventricle). For SP delineation from these adjacent layers based on combined cytological criteria, we analyzed the sublaminar distribution of different microstructural elements and the associated maturational gradients throughout development, using immunocytochemical and histological techniques on postmortem brain material (Zagreb Neuroembryological Collection). The analysis revealed that the SP compartment of the lateral neocortex shows changes in laminar organization throughout fetal development: the monolayer in the early fetal period (presubplate) undergoes dramatic bilaminar transformation between 13 and 15 postconceptional weeks (PCW), followed by subtle sublamination in three ‘floors’ (deep, intermediate, superficial) of midgestation (15–21 PCW). During the stationary phase (22–28 PCW), SP persists as a trilaminar compartment, gradually losing its sublaminar organization towards the end of gestation and remains as a single layer of SP remnant in the newborn brain. Based on these sublaminar transformations, we have documented developmental changes in the distribution, maturational gradients and expression of molecular markers in SP synapses, transitional forms of astroglia, neurons and ECM, which occur concomitantly with the ingrowth of thalamo‐cortical, basal forebrain and cortico‐cortical axons in a deep to superficial fashion. The deep SP is the zone of ingrowing axons – ‘entrance (ingrowth) zone’. The process of axonal ingrowth begins with thalamo‐cortical fibers and basal forebrain afferents, indicating an oblique geometry. During the later fetal period, deep SP receives long cortico‐cortical axons exhibiting a tangential geometry. Intermediate SP (‘proper’) is the navigation and ‘nexus’ sublamina consisting of a plexiform arrangement of cellular elements providing guidance and substrate for axonal growth, and also containing transient connectivity of dendrites and axons in a tangential plane without radial boundaries immersed in an ECM‐rich continuum. Superficial SP is the axonal accumulation (‘waiting compartment’) and target selection zone, indicating a dense distribution of synaptic markers, accumulation of thalamo‐cortical axons (around 20 PCW), overlapping with dendrites from layer VI neurons. In the late preterm brain period, superficial SP contains a chondroitin sulfate non‐immunoreactive band. The developmental dynamics for the distribution of neuronal, glial and ECM markers comply with sequential ingrowth of afferents in three levels of SP: ECM and synaptic markers shift from deep to superficial SP, with transient forms of glia following this arrangement, and calretinin neurons are concentrated in the SP during the formation phase. These results indicate developmental and morphogenetic roles in the SP cellular (transient glia, neurons and synapses) and ECM framework, enabling the spatial accommodation, navigation and establishment of numerous connections of cortical pathways in the expanded human brain. The original findings of early developmental dynamics of transitional subtypes of astroglia, calretinin neurons, ECM and synaptic markers presented in the SP are interesting in the light of recent concepts concerning its functional and morphogenetic role and an increasing interest in SP as a prospective substrate of abnormalities in cortical circuitry, leading to a cognitive deficit in different neurodevelopmental disorders.     

维生素D3受体在人胎脑表达的研究

为研究维生素D3受体(VDR)在正常人胎脑的分布,进而探讨1,25-二羟维生素D3[1,25-(OH)2D3]与正常人胎脑发育的关系,本实验按合法程序收集2～7月龄正常人胎脑,用免疫组织化学方法研究VDR在正常人胎脑的时空表达情况。结果显示:阳性产物在海马结构存在于胞核,3月龄出现表达的高峰,此后逐渐下降;在额叶皮质以及中脑部位的胞核和胞浆都可存在,其表达随胎龄增长。以上结果表明VDR在2～7月龄的人胎脑额叶皮质、海马结构和中脑有表达,且各部位的表达模式不同,提示1,25-(OH)2D3通过VDR可在人胎脑不同部位发育中发挥作用。     

Morphological study of the perireticular nucleus in human fetal brains

Abstract The perireticular nucleus consists of scattered neurons that are located in the internal capsule. The presence of perireticular neurons in the rat, ferret, cat and human has been described previously. Evidence suggests that the perireticular neurons in various species decrease in number with increasing gestation, but in humans this finding has not been supported by quantitative data. This study aimed to investigate (1) the morphology of the human fetal perireticular neurons, (2) the average number of perireticular neurons within the anterior and posterior crus of the internal capsule per unit area, and (3) the magnitude and the stage of neuronal loss in the human perireticular nucleus subsequent to maturation. Nissl-stained sections of the internal capsule of human fetal brains of 24, 26.5, 32, 35, 37 and 39 weeks of gestation showed a number of clearly distinguishable large perireticular and small microglia cells. A regular increase of both perireticular and microglial cells was observed up to 32 weeks of gestation, after which a dramatic reduction in the number of both perireticular and microglia cells was observed. The average number of perireticular and the microglia cells per unit area, located within the posterior crus, was more than in the anterior crus of the internal capsule. In the adult, no perireticular neurons were detected within the internal capsule. The results show that perireticular neurons are not restricted to the region lateral to the thalamus and medial to the globus pallidus (posterior crus) but are also present at the region lateral to the caudate nucleus and medial to the globus pallidus (anterior crus).     

The total number of white matter interstitial neurons in the human brain

In the adult human brain, the interstitial neurons (WMIN) of the subcortical white matter are the surviving remnants of the fetal subplate zone. It has been suggested that they perform certain important functions and may be involved in the pathogenesis of several neurological and psychiatric disorders. However, many important features of this class of human cortical neurons remain insufficiently explored. In this study, we analyzed the total number, and regional and topological distribution of WMIN in the adult human subcortical white matter, using a combined immunocytochemical (NeuN) and stereological approaches. We found that the average number of WMIN in 1 mm³ of the subcortical white matter is 1.230 ± 549, which translates to the average total number of 593 811 183.6 ± 264 849 443.35 of WMIN in the entire subcortical telencephalic white matter. While there were no significant differences in their regional distribution, the lowest number of WMIN has been consistently observed in the limbic cortex, and the highest number in the frontal cortex. With respect to their topological distribution, the WMIN were consistently more numerous within gyral crowns, less numerous along gyral walls and least numerous at the bottom of cortical sulci (where they occupy a narrow and compact zone below the cortical‐white matter border). The topological location of WMIN is also significantly correlated with their morphology: pyramidal and multipolar forms are the most numerous within gyral crowns, whereas bipolar forms predominate at the bottom of cortical sulci. Our results indicate that WMIN represent substantial neuronal population in the adult human cerebral cortex (e.g. more numerous than thalamic or basal ganglia neurons) and thus deserve more detailed morphological and functional investigations in the future.     

应用DTI技术对人脑白质纤维束的初步研究

目的建立扩散张量纤维束成像对人脑白质纤维的显示方法,并应用中国数字化可视人体数据进行对照观察,验证扩散张量成像(DTI)方法的可靠性。方法选择5名健康志愿者进行DTI成像,采用DtiStudio软件进行分析处理,重建出部分各向异性(FA)图、容积比(VR)图、相对各向异性(RA)图、表面扩散系数(ADC)图以及二维彩色张量图。应用中国数字化可视人体数据集断面图像、FA图及彩色FA图进行对照观察,利用fibertracking纤维跟踪软件及3DMRI软件进行三维重建显示脑内主要白质纤维束,辨认脑内白质纤维束的位置、形态。结果应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,包括联络纤维如弓形纤维、钩束、扣带束、上纵束和下纵束,连合纤维如胼胝体、前连合和穹隆,投射纤维如锥体束、视放射、内侧丘系等。DTI纤维束成像结果与已知解剖知识、中国可视化人体断面图像具有很好的一致性。结论应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,其结果与中国可视化人体断面图像、已知解剖知识是一致的,应用DTI纤维束成像研究脑内纤维连通性是可靠的。     

胎脑与成年脑皮质组织的蛋白质组学分析

目的 应用蛋白质组技术研究成年和胚胎脑皮质蛋白质组表达差异,初步探索在胎脑与成年人中脑蛋白的变化情况.方法 收集成人无病变区正常脑皮质1份和水囊引产胎脑组织脑皮质2份(3月胎脑组织和5月胎脑组织),提取总蛋白,通过双相电泳分离蛋白,每组样品均重复电泳,使用PDQuest7.0图像分析软件分析电泳图谱,得到具有表达差异的蛋白质,分别选取在大脑发育过程中逐步降低和逐步升高的差异点及在胎脑成脑蛋白表达中差异两倍以上的蛋白点,应用胶内酶切和基质辅助激光解析电离飞行时间质谱(matrix-assisted laser desorption/ionization-time of flight-time of flight,MALDI-TOF-TOF)进行鉴定,得到肽指纹图谱,并查阅蛋白质数据库得到蛋白质的相关信息.结果 (1)成人脑组织、3月胎脑组织和5月胎脑组织的脑组织蛋白图谱分别测得642、511和527个点,图象匹配率达87%.成人脑蛋白图谱中碱性蛋白点明显多于胎脑的;(2)成人脑组织、3月胎脑组织和5月胎脑组织的脑组织单独特有蛋白分别为:172、171和152个;(3)与成人脑组织比较,3月胎脑组织和5月胎脑组织的差异蛋白质分别为131和115个;差异在2倍以上的蛋白点为60和40个,其中低表达的蛋白点分别有24和17个,高表达蛋白点为36和23个;(4)白蛋白、磷酸丙糖异构酶等8种蛋白表达均有不同的变化.脂肪酸结合蛋白7和未命名蛋白只在3月胎脑高表达,而5月胎脑和成人组均无表达;核酮糖1,5-二磷酸羧化酶/加氧酶和转导素只在成人脑中高表达,胎脑无表达.血清白蛋白却随着大脑发育逐渐降低.ATP合成酶、线粒体F0复合体亚基、磷酸丙糖异构酶随着大脑发育而逐渐升高.结论 人类从胚胎期到成人发育过程中脑部蛋白质可能会发生明显改变,这些差异蛋白的发现为研究脑发育机理提供了极其有益的线索.

Abstract：

Objective To study the differences of protein expression levels in the brain cortex of human fetus and adult with proteomics technique, and provide preliminary data on the change of proteins during brain development. Methods Proteins extracted from human temporal lobes in fetal (3 month and 5 month respectively) and adult (30 years old) brain were separated by two-dimensional gel electrophoresis (2DE).The proteins were then stained with colloidal Coomassie blue to produce a high-resolution map of the proteiome.The differential protein spots were analyzed by PDQuest 7.0 software and 8 spots,which were gradually reduced or gradually increased in brain development process and the protein spots of difference over two-fold in the brain,were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF).Results (1) On average, 642, 511 and 527 protein spots could be obtained in the temporal lobes of adult, 3 month and 5 month fetus. The matching rate of images was 87%. The basic proteins in adult brain were obviously much more than that in the fetus; (2) There were 172, 171 and 152 singular protein spots in temporal lobes of adult, 3 month and 5 month fetus respectively. (3) Compared with adult, there were 131 and 115 different protein spots in the 3 month and 5 month fetus respectively. There were 60 and 40 protein spots with more than 2 fold difference, among which 24 and 17 were down-regulated, and 36 and 23 were up-regulated respectively. (4) There was different expression in proteins such as serum albumin, triosephosphate isomerase, etc. in the 3 groups. Fatty acid binding protein 7 and unnamed proteins were only highly expressed in the 3 month brain;ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit and transducin beta-1 subunit were up-regulated in adult brain. Serum albumin decreases gradually with brain development. However, ATP synthase, mitochondrial F0 complex, and triosephosphate isomerase increase gradually with brain development. Conclusion The proteins of human brain cortex were obviously changed from embryonic stage to adult. The differentially displayed proteins may provide further insight into the understanding of development of human brain.     

Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury

Mild traumatic brain injuries (TBI) are common in athletes, military personnel, and the elderly, and increasing evidence indicates that these injuries have long-term health effects. However, the difficulty in detecting these mild injuries in vivo is a significant impediment to understanding the underlying pathology and treating mild TBI. In the following experiments, we present the results of diffusion tensor imaging (DTI) and histological analysis of a model of mild repetitive closed-skull brain injury in mouse. Histological markers used included silver staining and amyloid precursor protein (APP) immunohistochemistry to detect axonal injury, and Iba-1 immunohistochemistry to assess microglial activation. At 24h post-injury, before silver staining or microglial abnormalities were apparent by histology, no significant changes in any of the DTI parameters were observed within white matter. At 7 days post-injury we observed a reduction in axial and mean diffusivity. Relative anisotropy at 7 days correlated strongly with the degree of silver staining. Interestingly, APP was not observed at any timepoint examined. In addition to the white matter alterations, mean diffusivity was elevated in ipsilateral cortex at 24h but returned to sham levels by 7 days. Altogether, this demonstrates that DTI is a sensitive method for detecting axonal injury despite a lack of conventional APP pathology. Further, this reflects a need to better understand the histological basis for DTI signal changes in mild TBI.     

人胎儿中枢神经系统凋亡抑制因子bcl-2mRNA的发育

目的 研究人胎儿中枢神经系统凋亡抑制因子bcl-2mRNA的发育表达。方法 用地高辛标记的bcl-2 cRNA探针原位杂交组织化学技术，检测了12—39周胎儿中枢神经系统内bcl-2 mRNA的表达情况。结果 ①在所检测的各脑区均有bcl-2 mRNA表达。第12周，有强阳性的bcl-2 mRNA出现在脊髓、延髓的运动神经元、大脑额叶的皮质板；小脑和大脑室层的bcl-2 mRNA表达较弱。bcl-2 mRNA的水平一般是随胎龄的增长而下降，至第39周表达最弱。②bcl-2 mRNA主要在神经元表达。结论 在人胎儿神经系统发育中表达的bcl-2可能与编程性细胞死亡有关。     

应用弥散张量成像技术检测慢性原发性闭角型青光眼患者脑白质结构

目的 采用磁共振弥散张量成像(DTI)检测慢性闭角型青光眼(PACG)患者脑白质病变,用各向异性指数(FA)改变分析病变部位。方法 回顾性分析2008-2009年在天津医科大学总医院眼科就诊并行颅脑MRI检查患者的临床资料,其中确诊为慢性PACG并同时行DTI扫描的患者25例为慢性PACG组,根据视野损害程度分为轻度组和重度组;选取同一时间段行颅脑DTI扫描的健康人25例为正常对照组。采用FSL和DTIstudio软件处理原始数据得到FA图,输入SPM5软件做标准化处理,然后进行灰白质分割,对分割后的白质FA图进行平滑处理,最后对慢性PACG组和正常对照组FA图进行两样本t检验比较,采用FWE方法校正统计结果,取P＜0.05有统计学意义,将结果叠加于标准模板,显示阈值设定为10个体素。采用同样方法分析慢性PACG轻度组和重度组FA图差异。结果剔除头动明显受试者图像后,慢性PACG组和正常对照组各有22例入组,慢性PACG组分为轻度组13例、重度组9例。与正常对照组比较,慢性PACG患者双侧视束脚周段FA值明显降低(P＜0.05,FWE校正),左侧包含98个体素,右侧包含56个体素。慢性PACG轻度组与重度组FA值差异无统计学意义(P＞0.05)。结论 DTI可检测慢性PACG患者脑白质结构病变。FA值可反应双侧视束脚周段病变。     

磁共振扩散张量成像评价小儿脑病的初步应用

目的应用扩散张量成像（DTI）来进一步评价小儿脑疾病，探讨DTI的诊断价值。方法对15例患各种脑病的小儿进行MRI检查，其中男性10例，女性5例，年龄为生后3天至11岁（平均年龄4．8岁）。采用Philips Intera Achieva 3．0 Tesla的超导MRI仪，用回波平面成像（EPI）的DTI技术，b为800s／mm^2，15个方向。观察彩色分数各向异性（FA）图和三维彩色编码图。结果15例患儿中，发育畸形2例，分别是胼胝体发育不良、巨脑回；脑室旁白质软化（PVL）7例；缺氧缺血性脑病3例；脑软化2例；脑积水1例。在巨脑回病例，常规MRI见右侧脑回发育不良，呈巨脑回畸形，右侧脑室扩大，在DTI上见右侧病变区白质束明显较对侧少。胼胝体发育不良病例在DTI张量图见胼胝体菲薄。在PVL和缺氧缺血性脑病病例均可见白质纤维束在放射冠颜色混杂，方向性混乱。脑软化病例可见白质纤维束部分中断。在脑积水病例可见白质束受压推移。结论DTI能够显示白质束的走向、绕行、交叉及推挤、中断等异常，可能对今后评估小儿脑病的预后转归有帮助。     

Populations of subplate and interstitial neurons in fetal and adult human telencephalon

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular) interstitial neurons in the postnatal and adult deep cerebral white matter (i.e. corpus callosum, anterior commissure, internal and external capsule and the corona radiata/centrum semiovale). Although these deep interstitial neurons are poorly developed or absent in the brains of rodents, they represent a prominent feature of the significantly enlarged white matter of human and non-human primate brains.     

Discrimination between glioblastoma multiforme and solitary metastasis using morphological features derived from the p:q tensor decomposition of diffusion tensor imaging

The management and treatment of high‐grade glioblastoma multiforme (GBM) and solitary metastasis (MET) are very different and influence the prognosis and subsequent clinical outcomes. In the case of a solitary MET, diagnosis using conventional radiology can be equivocal. Currently, a definitive diagnosis is based on histopathological analysis on a biopsy sample. Here, we present a computerised decision support framework for discrimination between GBM and solitary MET using MRI, which includes: (i) a semi‐automatic segmentation method based on diffusion tensor imaging; (ii) two‐dimensional morphological feature extraction and selection; and (iii) a pattern recognition module for automated tumour classification. Ground truth was provided by histopathological analysis from pre‐treatment stereotactic biopsy or at surgical resection. Our two‐dimensional morphological analysis outperforms previous methods with high cross‐validation accuracy of 97.9% and area under the receiver operating characteristic curve of 0.975 using a neural networks‐based classifier. Copyright © 2014 John Wiley & Sons, Ltd.     

Early development of the cortical layers in the human brain

The cortical plate (CP) first appears at seven postconceptional weeks (pcw), when it splits the preexisting preplate into two layers, the marginal zone and the presubplate (pSP). Although three-dimensional (3D) analysis using fetal magnetic resonance imaging and two-dimensional tissue observations have been reported, there have been no studies analyzing the early development of the layer structure corresponding to the pSP stage in 3D. Here, we reconstructed 3-D models of the brain with a focus on the cortical layers in pSP stage. To achieve this, we digitized serial tissue sections of embryos between CS20 and CS23 from the Kyoto Collection (n = 7, approximately 7–8.5 pcw), and specimens at early fetal phase from the Blechschmidt Collection (n = 2, approximately 9.5–12 pcw, crown rump length [CRL] 39 and 64 mm). We observed tissue sections and 3D images and performed quantitative analysis of the thickness, surface area, and volume. Because the boundary between pSP and the intermediate zone (IZ) could not be distinguished in hematoxylin and eosin-stained sections, the two layers were analyzed together as a single layer in this study. The histology of the layers was observed from CS21 and became distinct at CS22. Subsequently, we observed the 3-D models; pSP-IZ was present in a midlateral region of the cerebral wall at CS21, and an expansion centered around this region was observed after CS22. We observed it over the entire cerebral hemisphere at early fetal phase (CRL 39 mm). The thickness of pSP-IZ was visible in 3D and was greater in the midlateral region. At the end of the pSP stage (CRL 64 mm), the thick region expanded to lateral, superior, and posterior regions around the primordium of the insula. While, the region near the basal ganglia was not included in the thickest 10% of the pSP-IZ area. Middle cerebral artery was found in the midlateral region of the cerebral wall, near the area where pSP-IZ was observed. Feature of layer structure growth was revealed by quantitative assessment as thickness, surface area, and volume. The maximum thickness value of pSP-IZ and CP increased significantly according to CRL, whereas the median value increased slightly. The layer structure appeared to grow and spread thin, rather than thickening during early development, which is characteristic during pSP stages. The surface area of the cerebral total tissue, CP, and pSP-IZ increased in proportion to the square of CRL. The surface area of CP and pSP-IZ approached that of the total tissue at the end of the pSP stage. Volume of each layer increased in proportion to the cube of CRL. pSP-IZ and CP constituted over 50% of the total tissue in volume at the end of the pSP stages. We could visualize the growth of pSP-IZ in 3D and quantify it during pSP stage. Our approach allowed us to observe the process of rapid expansion of pSP-IZ from the midlateral regions of the cerebral wall, which subsequently becomes the insula.     

Structural organization of the prefrontal white matter pathways in the adult and aging brain measured by diffusion tensor imaging

Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of frontal callosal fibers to normal aging. The present study extended this examination systematically to other prefrontal white matter regions. Structural magnetic resonance imaging and DTI datasets were acquired from 69 healthy subjects aged 22–84 years. The prefrontal white matter was parcellated into several anatomical sub-regions: medial and lateral orbitofrontal white matter, dorsolateral prefrontal white matter, and medial prefrontal white matter, using reliable DTI-tractography protocols. Tract-specific characteristics were calculated using Matlab. Regression models were used to determine the relationship between age and structural integrity of white matter tracts. The results of our study demonstrate regional age-related changes in the prefrontal white matter tracts of the human brain. This study was cross-sectional and therefore additional longitudinal studies are needed to confirm our findings.     

Corticoreticular pathway in the human brain: diffusion tensor tractography study

LINGO-1 (leucine rich repeat and Ig domain containing Nogo receptor interacting protein-1) is a central nervous system transmembrane protein which simultaneously interacts with the Nogo-66 receptor and p75^NTR or TROY on neurons to form a receptor complex responsible for myelin-mediated neurite outgrowth inhibition. On oligodendroglial cells, LINGO-1 interacts with p75^NTR to constitutively inhibit multiple aspects of oligodendrocyte differentiation. Recently, LINGO-1 was identified as an in vivo interacting partner of the amyloid precursor protein (APP) and, correspondingly, cellular LINGO-1 expression was found to augment the release of the Abeta peptide, the potential causative agent of Alzheimer's disease. In addition, the recombinant LINGO-1 ectodomain has been shown to self-interact in solution and after crystallisation. Here, we have used deletional mutagenesis to identify the regions on LINGO-1 that are involved in homo- and heterotypic interactions. We have found that the N-terminal region containing the leucine-rich repeats along with the transmembrane and cytoplasmic domains of LINGO-1 are not required for self-interaction or interaction with APP.     

Fronto-striatal connections in the human brain: a probabilistic diffusion tractography study

Anatomical studies in animals have described multiple striatal circuits and suggested that sub-components of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain, we used Diffusion Tensor Imaging (DTI) tractography to reconstruct neural connections between the frontal cortex and the caudate nucleus and putamen in vivo. We demonstrate that the human caudate nucleus is interconnected with the prefrontal cortex, inferior and middle temporal gyrus, frontal eye fields, cerebellum and thalamus; the putamen is interconnected with the prefrontal cortex, primary motor area, primary somatosensory cortex, supplementary motor area, premotor area, cerebellum and thalamus. A connectivity-based seed classification analysis identified connections between the dorsolateral prefrontal areas (DLPFC) and the dorsal-posterior caudate nucleus and between the ventrolateral prefrontal areas (VLPFC) and the ventral-anterior caudate nucleus. For the putamen, connections exist between the supplementary motor area (SMA) and dorsal-posterior putamen while the premotor area projects to medial putamen, and the primary motor area to the lateral putamen. Identifying the anatomical organization of the fronto-striatal network has important implications for understanding basal ganglia function and associated disease processes.