| The human cerebellum, located at the lower back of the brain, whose function is now being reappraised. Formerly this structure was thought to have only a motor function, and chiefly involved in sensory, coordination and control motor activities. But during the past two decades a broader view of its function has emerged as a result of new research, and now the cerebellum is regarded as a structure that participated in learning, motor planning, sensor processing, cognition and emotion functions.Firstly, for a long time, there are only very few researches available concerning the differential roles of the cerebellar cortex and nuclei in human brain lesion and functional imaging studies. With the development of functional imaging researches and clinical applications in the deep cerebellar nuclei, to discriminate the precise positions of the deep cerebellar nuclei are necessary for functional research on the cerebellum and stereotactic operation of the correlative motor disorders. However, to characterize the deep cerebellar nuclei in vivo is difficult, because they can not been clearly distinguished on the routine MRI sequences. There is still no "gold standard" histological or imaging method existing to confirm that the identified regions on MR images correspond with real structures.In the first part of our research, the dentate, as well as fastigial, globose and emboliform nuclei can be clearly delineated on successive thin postmortem sections and 3T MR images. Furthermore, the section-based 3D model and normalized MRI data will provide standard reference for functional imaging researches and clinical applications in the deep cerebellar nuclei.Secondly, mounting evidences from previous histological, neuroimaging, and behavioral studies revealed sex-related differences in the cerebellar structure, development, function, behavior and developmental neuropsychiatric disorders, recently. In addition, the human cerebellum is not only structurally asymmetric, but also functionally asymmetric. Thus far the reported findings about gender-related cerebellar differences and asymmetry in human cerebellum in postmortem histological or magnetic resonance imaging (MRI) studies are anatomically unspecific and inconsistent. Therefore, the effects of gender and asymmetric patterns of cerebellum are still in a state of dispute not only at the global but regional level, which needs to be specifically uncovered.In the second part of our research, we revealed detailed morphologic knowledge of gender-related differences and asymmetric patterns in normal human cerebellum, which could provide a normal volumetric database of human cerebellum to understand structural underpinning for the sexual dimorphisms and asymmetric changes exhibited by the normal and diseased cerebellum.For the past decade, the complex network theory was applied in different scientific fields including neuroscience. From different scales, the brain has evolved into a complex network to support rapid information processing. Small-world architectures have been found in several empirical studies of structural and functional brain networks in humans and other animals, and over a wide range of scales in space and time. Recently, the morphometry-based connection concept has been proposed using various morphological indices (e.g. cortical thickness, area, volume, complexity etc.) to characterize the underlying organizational patterns of the brain structural networks, and demonstrated similar small world network topological properties in human brain. Meanwhile, the modularity, another important feather of the complex system, was also estimated in the structural brain network and had a great overlap with the functional modules. The correspondence between anatomical landmarks and functional areas is still poorly understood within the cerebellum as compared with the cerebral cortex. However, mounting evidences from the cerebellar connectivity and function studies suggest that the functional map in the cerebellar cortex is likely to be as rich and complex as that in the cerebral cortex. On the basis of the anatomical and connections of human cerebellum, we hypothesized that there might be an interacting, complex network in cerebellum reflecting its coordination roles in preparing internal conditions for imminent information acquisition, analysis, or action.In the third part of our research, by using graph theory analyses, we explored the structural connectivity patterns in human cerebellum using volumetric measurements. For the first time, we demonstrated that the human cerebellum networks also had a typical'small-world'topology as well as cerebral cortex with high clustering of local connections and a short minimum path length between any pair of regions. The results might provide substrate evidences to disclose the correlations between cerebellar morphology and function for the future research. Furthermore, we demonstrated the differences in the cerebellum structural networks derived from gray matter volume between the male and female groups. Such new insight could provide important implications for understanding gender effects on the cerebellar anatomy and function.The three parts of our research are as follows:Delineation and Visualization of Human Deep Cerebellar Nuclei by Thin Postmortem Sections and MRIObjectives:Our research aimed to discriminate the deep cerebellar nuclei on the serial thin postmortem sections with MRI correlation and create a three-dimensional visualization model, which could provide anatomic reference for the functional imaging research and stereotactic operation of human cerebellum.Subjects and Methods:After MRI examination to exclude organic lesions, two head specimen were selected for this study. After being embeded with gelatin and preserved under profound hypothermia (-30°), the specimen was sliced into 0.1mm transverse sections along inter-commissural line with SKC 500 computerized freezing milling machine. Then the sections were photographed by a high-resolution digital camera and saved for the delineation and visualization. The high resolution MR images the oher postmortem were acquired using 3.0Tesla MRI scanner with a 3D sequence and then normalized into Talairach space. All the representative sections were carefully delineated, and the equivalent MR images and in vivo MR images were selected for comparison with sectional images to predict the location of the cerebellar nuclei in the normalized space. The anatomic structures of interest were observed in two-dimensional sections and MR images, then segmented and reconstructed three-dimensionally.Results:1. The transverse sections involving with cerebellum about 620 layers were obtained and among the total, dentate nucleus, fastigial nucleus, globose nucleus and emboliform nucleus occurred in about 145,12,25 and 20 layers respectively.2. The nuclei were four in number on either side, the dentate nucleus localized on majority of the thin sections and appeared as a convoluted band of gray matter. The nucleus fastigii was situated to the middle line at the anterior end of the superior vermis, and over the roof of the fourth ventricle. The emboliform nucleus lay immediately to the medial side of the dentate nucleus, and partly covering its hilus. The globose nucleus was an elongated mass, directed antero-posteriorly, and placed medial to the emboliform nucleus.3. The position and morphology of the deep cerebellar nuclei could be clearly illustrated in the 2D images and 3D visualization models.Conclusions:The position and morphometry of the deep cerebellar nuclei could be observed clearly on the successive thin sections and MRI data. The section-based 3D model and normalized MRI data could provide standard reference for functional imaging researches and clinical applications in the deep cerebellar nuclei. Sexual Dimorphism and Asymmetry in Human Cerebellum:an MRI-based Morphometric StudyObjectives:The purpose of this study is firstly to obtain more precise quantitative neuroimaging data of human cerebellum, and then to reveal gender effects and asymmetrical properties on human cerebellum.Subjects and Methods:The present study includes 112 neurologically normal adults (males/females:66/46; age:18-33 years), all right-handed, were selected from the database of Chinese Standard Brain Atlas project. An optimized vox el-based morphometry (VBM) in spatial unbiased infratentorial template (SUIT) space together with an automated atlas-based volumetric approach as a validation was performed for mapping regional GM gender-related differences across the whole cerebellum. The asymmetric properties of cerebellar hemisphere and the interactions with sex effect were also accessed by VBM analysis.Results:1. In terms of the global effects of sex, the male group (111.73±14.11cm3) had significantly larger mean cerebellar GM volume (without controlling TIV) than the female group (102.89±11.45cm3).2. For the regional differences, significant gender effects in cerebellar GM were observed in anterior and middle posterior lobes greater in male and lateral posterior lobe greater in female.3. With the created symmetric cerebellar template, the asymmetric properties of cerebellar hemisphere were also accessed by VBM analysis, showing rightward asymmetry distributed in most cerebellar lobules and leftwards asymmetry distributed in the lobules around medial posterior lobe.4. In addition, gender differences in males showed higher leftward asymmetry sparsely within a few lobules and lower rightward asymmetry mainly within lobule CrusⅡ, as compared with females.Conclusions:The present study revealed detailed morphologic knowledge of gender-related differences and asymmetric patterns in the cerebellum of young Chinese adults, which could provide a normal volumetric database of human cerebellum to understand structural underpinning for the sexual dimorphisms and asymmetric changes exhibited by the normal and diseased cerebellum.Graph Theoretical Analysis and Gender Effect in Human Cerebellum Structural NetworkObjectives:In this research, by using graph theory analyses, we try to characterize the structural connectivity pattern in human cerebellum using volumetric measurements from in vivo MRI. Furthermore, we try to reveal the differences in the cerebellum structural networks derived from gray matter volume between the male and female groups.Subjects and Methods:Here, we characterized the underlying organization of structural connectivity patterns in human cerebellum from a large sample of 112 young, healthy Chinese adults using graph theoretical analysis. The cerebellar cortex was partitioned into 28 sub-regions, each defined as a network node, and two areas were considered structurally connected if they showed statistically significant correlations in their volumes. Furthermore, two typical matrixes were calculated, i.e. characteristic path length and clustering coefficient, to verify our hypothesis. And then, we revealed the degree distribution and defined the hub regions in the cerebellum network.Moreover, the acquired normalized gray matter volumes of 28 cerebellar lobules were applied to construct two binarized structural cerebellum networks for both groups by measuring the Pearson correlation coefficients between every pair of cerebellar regions across all subjects after removing the effects of age, gender and age-gender interaction. Finally, using a permutation test, we evaluated the effects of gender on the small world properties of structural cerebellum network.Results:1. We demonstrated that the human cerebellum networks also had a typical 'small-world'topology as well as cerebral cortex with high clustering of local connections and a short minimum path length between any pair of regions.2. In addition, the degree distribution followed an exponentially truncated power-law form and the structural hubs of the cerebellum networks were defined by calculation both the node degree and betweenness centrality.3. Similar global efficiency in both genders and a significant greater local efficiency (higher Cluster coefficient) in female, suggesting that the cerebellar networks in males and females exhibited similar function but with different architectures.4. Gender-related effects on nodal betweenness centrality were found at several cerebellar regions, including Vermis_CrusⅡ, Right_CrusⅡ, Vermis_Ⅹhigher in male and Left_Ⅴ, Right_Ⅵhigher in female. Moreover, Hub regions distribute differently in male and female cerebellum networks at a sparsity of 21%.Conclusions:To our knowledge, this is the first study to explore the structural connectivity patterns in human cerebellum using volumetric measurements. The constructed cerebellar structural network could provide new evidences to disclose the correlations between cerebellar morphology and function. Moreover, we also demonstrated the differences in the cerebellar structural networks between the male and female groups, which could provide new insights and implications for understanding gender effects on the human cerebellum. |
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