人类大脑左右半球在结构和功能上的不对称现象称为偏侧化，是神经科学的核心课题之一。近年来发展起来的功能磁共振技术和结构磁共振技术，尤其是人脑连接组学出现，为在活体人群上从系统角度验证大脑结构和功能的偏侧化提供技术支持。本工作报告通过结合弥散磁共振成像技术和复杂网络分析方法，开展了人类大脑半球白质网络的偏侧化研究。

半脑白质网络偏侧化发育老化研究。本部分的研究从发展和老化两个角度，系统地探索了疾病下人脑半球白质网络偏侧化随着年龄的发展和老化过程中的变化。在发育层面，通过分析ABIDE II公共数据库中的58名右利手男性自闭症谱系患者和70名年龄性别相匹配的正常发育被试，探索了ASD患者的半脑白质结构网络的偏侧化的异常发育轨迹。结果表明，随着年龄增长，正常发育被试组的半球白质网络效率右偏程度降低；而自闭症谱系患者组的网络效率偏侧化则不随年龄而变化，这种偏侧化异常主要来源于右半脑拓扑结构发育的异常晚熟。

在老化层面，探索了阿尔茨海默病患者的大脑半球白质网络拓扑属性的异常的偏侧化。结果发现，在全局属性层面，阿尔茨海默患者半球脑白质网络呈现异常的右偏拓扑不对称性。阿尔茨海默患者和轻度认知障碍患者半球脑白质网络节点效率右偏程度显著增加的区域主要在海马旁回和楔叶。左半球拓扑属性的改变是引起阿尔茨海默患者偏侧化异常的主要原因。

半脑白质连接的遗传基础研究。探讨左右半球的遗传基础的关系对于理解左右半球的偏侧化具有重要的理论意义。为了解决这个问题，在本研究中，我们使用高质量的扩散磁共振影像数据，结合双生子及家系信息，估计了同源左右白质连接的遗传度和遗传关联。结果表明，人类大脑左右半球具有相似的白质连接遗传度模式，同源白质连接的遗传因子（即半球间遗传关联）的重叠程度存在很大差异。特别是，皮层下白质连接的遗传度显著的高于皮质间白质连接，遗传因素在半球间完全重叠的机率也比皮层间的白质连接高。另外，长距离连接的遗传力和半球间遗传相关性强于短距离连接。这些发现强调了白质连接及其半球间关系的遗传学的决定因素，并为健康和疾病状态下白质连接的不对称性提供了遗传基础。

Human brain asymmetries have been well described. Intriguingly, a number of asymmetries in brain phenotypes have been shown to change throughout the lifespan. Recent studies have revealed topological asymmetries between hemispheric white matter networks in the human brain.

We systematically explored the atypical changes of the lateralization of the white matter network in the developmental and aging diseases. As the developmental disease, we revealed the atypical brain asymmetry/lateralization of white matter network for autism spectrum disorder (ASD). Here, the Autism Brain Imaging Data Exchange II database were used. White matter networks were constructed based the diffusion MRI and 3D T1 images. Statistical analyses revealed a decreased rightward asymmetry of network efficiencies with increasing age in the typical development group (TD), but not in the ASD group. More specifically, the TD group did not exhibit an age-related increase in network efficiency in the right hemisphere, but the ASD group did. In addition, we explored whether there was abnormal brain lateralization in aging disease. Specifically, we explored the abnormal lateralization of white matter network topological attributes in patients with Alzheimer's disease (AD). We found that the right hemispheric white matter network of Alzheimer's patients showed abnormal topological asymmetry, but the topological properties of the white matter network of patients with mild cognitive impairment and the normal elderly did not show lateralization. The node efficiency of right parahippocampal gyrus increased significantly in AD and MCI groups.

Answering the “Nature vs. Nurture” question of homologous structural phenotypes of the two hemispheres and their interhemispheric relation is a prerequisite for elucidating developmental mechanisms of brain asymmetries and related brain functions. In this part, we attempted to determine interhemispheric genetic relationships of interregional white matter (WM) connectivity. We showed that the heritability of WM connectivities was quite similar and coupled between the two hemispheres and that the degree of overlap in genetic factors underlying homologous WM connectivities varied substantially across the human brain. Intriguingly, subcortical WM connections showed stronger heritability and higher chance of interhemispheric complete overlap in genetic factors, compared with cortical WM connections. Moreover, there were length effects on these genetics of homologous left and right WM connectivities, with heritability higher and interhemispheric genetic correlations stronger for long-range connections than for short-range connections.