Heritability of Neuroanatomical Asymmetries in Primates

描述（由申请人提供）：半球专门化是指左右大脑半球的运动、知觉和认知功能的偏侧化。研究表明，神经解剖学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动物半球特化发育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展的独立和潜在的相互作用。值得注意的是，大脑不对称性的遗传性估计将在遗传相关的个体中计算，这些个体在生命的前三年中被一起或分开抚养。在拟议研究的第二部分中，将从灵长类动物中获得死后大脑，并对8个不同的Brodmann区域进行细胞结构分析。将为每只猿绘制个体细胞结构图，并将这些图与大脑模板进行配准。随后，将创建这些区域的概率图，并将其应用于与相同模板配准的体内MRI扫描的大样本（N > 290），以估计每个细胞构造区域的灰质体积。然后将计算整个样本中与已知谱系相关的灰质体积的遗传性估计。最后，将进行分析，以检查在体内和死后的大脑中的不对称性的变化是否与相关和不相关的个体之间的口面部运动控制相关。特别是，这些分析的目的是评估是否发展口面运动控制与生产故意发声的结果在初级和运动前皮质内的皮质重组。总的来说，这项研究的结果将提供关键信息的影响，遗传和早期饲养因素的发展和进化的灵长类动物的半球专业化。

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.