Cortical complexity in children with Autism unaffected Siblings and Controls

描述(申请人提供)：自闭症是一种严重的神经生物学疾病，具有强烈的遗传成分，出现在儿童早期。一些大脑结构异常与自闭症有关，尽管没有一个一直被复制，也没有在所有自闭症患者中看到单一的异常。这些不一致的一个可能原因是难以控制可能改变大脑形态的遗传和环境变量。在这项研究中，我们建议调查自闭症不协调的兄弟姐妹的皮质复杂性。这一研究群体将使我们能够对影响大脑发育的遗传和环境因素进行更大的实验控制。我们计划使用一种新颖的全脑皮质复杂性分析来评估大脑皮质形态和自闭症之间的关系，样本包括27对与自闭症不一致的同性兄弟姐妹，以及27名与自闭症参与者的兄弟姐妹年龄和性别匹配的典型发育中的参与者。此外，我们建议评估自闭症参与者的皮质折叠复杂性与行为特征之间的关系。最后，通过与19名自闭症儿童和13名年龄匹配的对照组(17-40个月大)的年轻样本进行比较，我们将能够评估自闭症患者从2岁到12岁的皮质折叠复杂性的发展轨迹。我们假设，与未受影响的兄弟姐妹和对照组相比，自闭症患者对社会认知、交流和面孔识别至关重要的大脑区域将发生变化。此外，我们假设这些区域的异常形态形态将与自闭症参与者的社交和沟通障碍的严重程度相关。我们进一步假设，与对照组相比，自闭症参与者在第二年至12岁期间，皮质折叠复杂性(形状随年龄变化)的发展将发生变化。这些信息将有助于明确哪些神经解剖学区域确实与自闭症有关，以及它们在整个童年时期是如何发展的。公共卫生相关性：虽然自闭症被公认为一种神经生物学疾病，但导致自闭症认知和行为障碍的具体神经发育途径尚不清楚。在这项拟议的研究中，我们将使用新的神经成像技术开始定义自闭症的有意义的生物学细分。更好地了解自闭症的神经生物学基础将使我们能够识别自闭症患者的亚群，从而开发出针对这种疾病的更有针对性的治疗方法。

DESCRIPTION (provided by applicant): Autism is a severe neurobiological condition with a strong genetic component that presents in early childhood. Several structural brain abnormalities have been associated with autism, though none have been consistently replicated and no single abnormality is seen in all persons with autism. A possible reason for these inconsistencies is the difficulty of controlling the genetic and environmental variables that can alter brain morphology. In this study, we propose to investigate cortical complexity in siblings discordant for autism. This study population will allow us to gain greater experimental control of genetic and environmental factors that influence brain development. We plan to use a novel, whole-brain analysis of cortical complexity to assess the relation between cortical brain morphology and autism in a sample of 27 same-gender sibling- pairs discordant for autism, as well as in 27 typically developing participant who are age- and gender- matched to the siblings of participants with autism. In addition, we propose to assess the relation between cortical folding complexity and behavioral features of autistic participants. Finally, by comparing results with a younger sample of 19 children with autism and 13 age-matched controls (17-40 months of age), we will be able to assess the developmental trajectory of cortical folding complexity in autism from the second year of life to 12 years of age. We hypothesize that brain regions important for social cognition, communication, and face recognition will be altered in autism as compared to their unaffected siblings and controls. In addition, we hypothesize that abnormal shape morphology in these regions will be correlated with the severity of social and communication impairments in participants with autism. We further hypothesize that development of cortical folding complexity (change of shape with age) will be altered between the second year of life and 12 years of age in participants with autism as compared to the control groups. This information will help to specify which neuroanatomical regions are indeed associated with autism, and how they develop throughout childhood. PUBLIC HEALTH RELEVANCE: Although autism is well recognized as a neurobiological condition, the specific neurodevelopmental pathways leading to the cognitive and behavioral disturbances in autism are unknown. In the proposed study, we will use novel neuroimaging techniques to begin to define meaningful biological sub-divisions of autism. A better understanding of the neurobiological underpinning of autism will allow to identify sub-groups of individuals with autism, leading to the development of more targeted treatments for this disorder.