Are aging outcomes worse for women with autism? Sex differences in the neurocircuitry of symptom camouflaging and its vulnerability to aging

7.项目摘要/摘要 患有自闭症谱系障碍(ASD)的女性表现出比男性更多的ASD特征补偿(称为 伪装)；要做到这一点，他们可能更多地利用认知控制和潜在的额叶-亚皮质 连通性。在我们的数据中，患有ASD的老年女性表现出较低的认知控制能力和较强的耦合性 认知控制和伪装之间的差异比男性更大；因此，年龄越大，对 女性ASD患者的症状表现明显高于男性。这项研究的长期目标是阐明 ASD症状表现寿命变化背后的生态和神经生物学机制。这个 这项建议的具体目标是1)在大范围内表征伪装与神经连接的相关性 成年男性和女性ASD样本和2)确定伪装易损性的性别差异 患有自闭症的老年人的大脑回路与衰老有关。意义：这项研究将确定性别- ASD伪装背后的特定大脑网络及其对衰老的脆弱性。调查结果将告知 对特征较少和易受伤害的老年自闭症患者进行基于生物学的干预。方法： AIM 1利用开放获取数据和来自我们实验室的数据；AIM 2将检查我们实验室持续的纵向数据 (2年和4年随访)。伪装将被定义为自我报告/观察到的ASD之间的差异 特征。大脑连通性将通过静息状态功能磁共振(FMRI)和扩散张量成像来测量。 沃尔什夫人立志成为一名研究生态和神经生物学的学术教授。 自闭症的补偿机制。她的长期目标是领导一个跨学科的临床实验室。 致力于基础科学和翻译科学，以改善ASD的成人结局。作为一种演讲语言 作为病理学家，她在ASD的儿科表型和社会行为的临床评估方面有经验。在……里面 在她的博士课程中，她获得了衰老和自闭症神经科学；功能磁共振成像分析；以及 神经心理评估。培训计划将实现以下目标，以补充她目前的 专长：1)高级神经成像分析(结构连通性、纵向脑变化和多部位 数据)；2)成人自闭症患者的表型；以及3)社会心理学理论和方法 自闭症患者的社会行为。神经成像和社会心理学方法的培训将主要在亚利桑那州进行 州立大学(ASU)。亚利桑那州立大学是一家享有盛誉的R1机构，与巴罗神经科合作 该研究所最先进的神经成像设备。ASD表型的培训将在西南部进行 自闭症研究和资源中心，一个致力于自闭症研究和临床护理的社区中心 生命的长短。这些机构为沃尔什夫人提供了满足她的培训的最佳支持环境 目标。他们处于ASD衰老研究的前沿，合作推出了首批纵向研究之一 成人自闭症患者认知和脑老化的研究。除了拟议的目标外，培训将侧重于 作为研究科学家的专业发展，并向更广泛的社区传播研究结果。

7. Project Summary/Abstract Women with autism spectrum disorder (ASD) show more compensation for ASD traits than men (termed camouflaging); to do so, they may capitalize more on cognitive control and underlying fronto-subcortical connectivity. In our data, older women with ASD show lower cognitive control abilities and a stronger coupling between cognitive control and camouflaging than men; thus, older age may have a more dramatic impact on symptom presentation in women with ASD than men. The long-term goal of this research is to elucidate the ecological and neurobiological mechanisms underlying lifespan changes in symptom presentation in ASD. The specific aims of this proposal are to 1) characterize the neural connectivity correlates of camouflaging in a large sample of adult men and women with ASD and 2) determine sex differences in the vulnerability of camouflaging and underlying brain circuits to aging in older adults with ASD. Significance: This study will identify the sex- specific brain networks underlying camouflaging in ASD and their vulnerability to aging. Findings will inform biologically-based interventions in the less characterized and vulnerable older adult cohort with ASD. Methods: Aim 1 leverages open-access data and data from our lab; Aim 2 will examine our lab’s ongoing longitudinal data (2 and 4 year follow-ups). Camouflaging will be defined as the discrepancy between self-report/observed ASD traits. Brain connectivity will be measured via resting-state functional MRI (fMRI) and diffusion tensor imaging. Mrs. Walsh aspires to become an academic professor investigating the ecological and neurobiological mechanisms of compensation in ASD. Her long-term goal is to lead an interdisciplinary clinical laboratory dedicated to basic and translational science to improve adult outcomes in ASD. As a speech language pathologist, she has experience in pediatric phenotyping of ASD and clinical assessment of social behavior. In her PhD program, she has gained expertise in aging and ASD neuroscience; fMRI analysis; and neuropsychological evaluation. The training plan will fulfill the following goals to complement her current expertise: 1) advanced neuroimaging analysis (structural connectivity, longitudinal brain changes, and multi-site data); 2) phenotyping in adults with ASD; and 3) social psychological theory and methods for characterizing social behavior in ASD. Training in neuroimaging and social psychology methods will occur primarily at Arizona State University (ASU). ASU is a well-regarded, R1 institution with collaborations at Barrow Neurological Institute’s state-of-the-art neuroimaging facilities. Training in phenotyping of ASD will occur at the Southwest Autism Research and Resource Center, a community center dedicated to ASD research and clinical care across the lifespan. These institutions provide optimal supportive environments for Mrs. Walsh to meet her training goals. They are at the forefront of aging research in ASD, collaboratively, launching one of the first longitudinal studies of cognitive and brain aging in adults with ASD. In addition to the proposed goals, training will focus on professional development as a research scientist and dissemination of findings to the broader community.