Macrostructural and Microstructural Analysis of the Primate Corpus Callosum

描述（由申请人提供）：了解胼胝体（CC）的连通性是一个重要的公共卫生目标，因为该结构被认为对人类高阶认知功能的出现至关重要。此外，CC大小的差异与许多神经精神和神经发育障碍有关，如精神分裂症、自闭症谱系障碍和图雷特综合症。评估脑CC大小变化的近似和最终机制对于理解其在各种人类认知和行为过程中的作用至关重要。在这个应用程序中，我们将研究两个不同的灵长类物种——黑猩猩（Pan troglodytes）和卷尾猴（Cebus apella）——的CC地形，它们独立地进化出了与人类共同的几个行为和解剖特征。具体目的是：1)利用MRI和DTI绘制卷尾猴和黑猩猩CC的解剖连通性；2)用死后标本评价卷尾猴和黑猩猩CC的组织学组织；3)验证DTI作为CC髓鞘形成和纤维取向通路的可靠和准确的标志物；4)复杂运动任务的行为测量与CC大小的个体差异之间的相关性。我们将结合脑成像（MRI和DTI）和社会生活对象（36只卷尾猴和36只黑猩猩）的行为测量，以及死后标本（8只卷尾猴和25只黑猩猩；这些受试者在运动任务中的表现的行为数据是可用的）的成像和组织学检查。我们假设黑猩猩（不包括卷尾猴）将呈现与人类相似的地形，与额叶皮层相关的区域约占CC纤维的2/3。卷尾猴与大脑额叶的纤维连接要少得多。然而，如果前皮层的地形在整个灵长目中都是保守的，那么卷尾猴应该表现出与黑猩猩（和人类）相似的组织。此外，我们期望发现性别和利手性对CC地形的影响，雌性和左撇子个体与雄性和右撇子个体相比，分别表现出不同的CC内纤维组成。我们进一步假设，运动学习半球间转移表现较好的受试者，其CC相对较大。

DESCRIPTION (provided by applicant): Understanding the connectivity of the corpus callosum (CC) is an important public health goal, as this structure is believed to be fundamentally important to the emergence of higher order cognitive functions in humans. Furthermore, differences in the size of the CC have been associated with a number of neuropsychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, and Tourette's syndrome. Evaluating the proximate and ultimate mechanisms that account for variation in CC size is crucial in understanding its role in a variety of human cognitive and behavioral processes. In this application, we will examine the topography of the CC in two divergent primate species - chimpanzees (Pan troglodytes) and capuchin monkeys (Cebus apella) - that have independently evolved several behavioral and anatomical characteristics in common with humans. Specific Aims are to 1) map the anatomical connectivity of the CC in capuchin monkeys and chimpanzees in vivo using MRI and DTI; 2) evaluate the histological organization of the CC in capuchin monkeys and chimpanzees using post-mortem specimens; 3) validate DTI as a reliable and accurate marker of myelination and fiber orientation pathways of the CC; and 4) correlate behavioral measures of complex motor tasks with individual differences in CC size. We will combine brain imaging (MRI and DTI) and behavioral measures in socially living subjects (36 capuchin monkeys and 36 chimpanzees) alongside imaging and histological examination of post-mortem specimens (8 capuchin monkeys and 25 chimpanzees; behavioral data of these subjects' performance on motor tasks is available). We hypothesize chimpanzees (but not capuchin monkeys) will show similar topography to humans, with regions associated with the frontal cortex to account for approximately 2/3 of CC fibers. Capuchins are expected to have significantly less fiber connections to the frontal lobe. However, if the topography of the CC is conserved across the primate Order, then capuchins should show similar organization as chimpanzees (and humans). Additionally, we expect to find sex and handedness effects on CC topography, with females and left-handed individuals showing different composition of the fibers within the CC compared to males and right-handed individuals, respectively. We further hypothesize that subjects who show better inter-hemispheric transfer of motor learning will have a relatively larger CC. PUBLIC HEALTH RELEVANCE: This research will examine the topography of the corpus callosum to evaluate the proximate and ultimate mechanisms that account for variation in the size of this structure. Individual differences in the size of the corpus callosum have been associated with a number of neuropsychiatric and neurodevelopmental disorders including schizophrenia, autism, and Tourette's syndrome. Thus, evaluating the mechanisms that influence corpus callosum size is critical to further our understanding of psychiatric conditions and neurodevelopmental disorders.