Heritability of Neuroanatomical Asymmetries in Primates

描述(申请人提供)：大脑半球特化是指大脑左右半球的运动、知觉和认知功能的侧化。研究表明，神经解剖和行为不对称模式的个体差异与各种临床问题有关，如严重精神病(精神分裂症)、神经发育障碍(如威廉综合征)、自闭症和口吃以及学习障碍(如诵读困难和特定语言障碍)。拟议研究的长期目标是确定影响灵长类大脑半球特化发展的遗传和非遗传机制。该提案的一个方面将评估遗传和早期社会养育因素对灵长类动物大脑不对称发育的独立和潜在的交互影响。值得注意的是，大脑不对称的遗传力估计将在基因相关的个体中计算，这些个体在出生后的头三年里一起或分开养育。在拟议的研究的第二部分，将从灵长类动物的身体脑中获取大脑，并对8个不同的布罗德曼区域进行细胞构筑分析。每个类人猿的单个细胞构筑图将被派生出来，并被登记到一个模板大脑中。随后，将创建这些区域的概率图，并将其应用于注册到同一模板的大样本在体MRI扫描(N&gt；290)，以便估计每个细胞结构区域的灰质体积。然后，将计算与已知家系相关的整个样本的灰质体积的遗传性估计。最后，将进行分析，以检验活体和死后大脑中不对称性的变化是否与相关和不相关个体的口面部运动控制有关。特别是，这些分析旨在评估与故意发声的产生相关的口面部运动控制的发展是否会导致初级和运动前皮质内的皮质重组。总而言之，这项研究的结果将提供关于遗传和早期养育因素对灵长类大脑半球特化发展和进化的影响的关键信息。

DESCRIPTION (provided by applicant): Hemispheric specialization refers to lateralized motor, perceptual and cognitive functions to the left and right cerebral hemispheres. Studies have shown that individual variation in patterns of neuroanatomical and behavioral asymmetries are associated with various clinical problems such as major psychoses (schizophrenia), neurodevelopmental disorders such as William's syndrome, autism and stuttering and learning disabilities such as dyslexia and specific language impairment. The long-term goals of the proposed studies are to identify the genetic and non-genetic mechanisms that influence the development of hemispheric specialization in primates. One aspect of the proposal will assess the independent and potential interactive effects of genetic and early social rearing factors on the development of brain asymmetries in primates. Notably, heritability estimates in brain asymmetries will be computed in genetically related individuals that have been reared together or apart during the first three years life. In a second part of the proposed studies, post-mortem brains will be obtained from primates and cytoarchitectonic analyses will be performed for 8 distinct Brodmann's regions. Individual cytoarchitectonic maps will be derived for each ape and these will be registered to a template brain. Subsequently probabilistic maps of these regions will be created and applied to a large sample of in vivo MRI scans (N > 290) registered to the same template in order to estimate grey matter volumes of each cytoarchtectonic region. Heritabilty estimates of the grey matter volumes will then computed in the entire sample in relation to known pedigrees. Lastly, analyses will be performed to examine whether variation in asymmetries in both in vivo and post-mortem brains are associated with oro- facial motor control among related and unrelated individuals. In particular, these analyses aim to assess whether developing oro-facial motor control associated with the production of intentional vocalizations results in cortical reorganization within the primary and premotor cortex. Collectively the results of this study will provide critical information on the influence of genetic and early rearing factors on both the development and evolution of hemispheric specialization in primates.