Anterior Cingulate and Fronto-Insular Related Brain Networks in Autism

描述（由申请人提供）：自闭症的特点是在相互的社会交往和沟通的质量障碍，与行为，兴趣和活动的限制，重复和刻板的模式。自闭症是一组被称为自闭症谱系障碍（ASD）的大脑发育障碍中最常见的病症，包括自闭症障碍、自闭症综合征和未另行说明的广泛性发育障碍。自闭症影响多达千分之六的儿童和成人。虽然医学科学已经取得了无数的里程碑式的进步，我们对自闭症的病理生理学的知识仍然非常有限。Von Economo神经元（VENs）是人类前扣带皮层（ACC）和额岛皮层（FI）中最丰富的大型双极纺锤形神经元，并且可能参与对复杂情况的快速和直观的评估。这些区域的VEN缺陷可能导致在社会背景下无法处理复杂的、不可预测的和新颖的信息。有证据表明，自闭症患者的行为缺陷与这些大脑区域的功能有关，这表明社交和认知能力的障碍可能与VENs的异常发育有关。我们建议调查异常的ACC和FI相关的大脑网络参与低层次的感觉和知觉和高层次的认知过程中的高功能ASD患者。我们假设，与正常对照组相比，ASD患者的ACC和FI在功能激活和连接异常方面存在核心缺陷。我们将利用一个改进的预期刺激范式以及共情和判断他人的疼痛任务，并采用多模态磁共振成像（MRI）方法，包括事件相关功能MRI，形态测量MRI和扩散张量成像来验证假设。我们还将探讨患者的成像数据与自闭症三个症状领域缺陷严重程度之间的关联。这种创新的方法涉及感觉/知觉和认知任务的整合，多模态神经成像和临床测试，以及将该项目与其他正在进行的直接研究神经元水平的VENS的研究联系起来，将提供对这种疾病的神经机制的具体和全面的功能和解剖学见解，这将启发我们在神经元和认知水平上对自闭症的理解，也可能指导新的治疗方法。公共卫生相关性：自闭症的特征是在相互的社会互动和沟通中存在质的障碍，具有受限制的，重复的和刻板的行为，兴趣和活动模式，影响多达千分之六的儿童和成人。虽然医学科学已经取得了无数的里程碑式的进步，我们对自闭症的病理生理学的知识仍然非常有限。这种创新的方法涉及感觉/知觉和认知任务，多模态神经成像和临床测试的整合，将提供具体和全面的功能和解剖学洞察这种疾病的神经机制，也可能指导新的治疗方法。

DESCRIPTION (provided by applicant): Autism is characterized as a qualitative impairment in reciprocal social interaction and communication, with a restricted, repetitive and stereotyped pattern of behavior, interest, and activities. Autism is the most common condition in a group of developmental disorders of the brain known as the autism spectrum disorders (ASDs), including autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified. Autism affects as many as six in a thousand children and adults. Although innumerable landmark advances have been achieved in the medical sciences, our knowledge about pathophysiology of autism is still very limited. Von Economo neurons (VENs) are large, bipolar, spindle shaped neurons that are most abundant in the human anterior cingulate cortex (ACC) and fronto-insular cortex (FI) and may be involved in the fast and intuitive assessment of complex situations. Deficiencies of VENs in these regions may result in the inability to process complex, unpredictable, and novel information in a social context. There is evidence linking the behavioral deficits observed in patients with autism to the functions of these brain regions, suggesting that the impairments of social and cognitive abilities may relate to abnormal development of VENs. We propose to investigate abnormalities of ACC- and FI-related brain networks involved in both low-level sensory and perceptual and high-level cognitive processes in high-functioning patients with ASD. We hypothesize that, compared to normal controls, there will be a core deficit in the ACC and FI in patients with ASD in terms of abnormal functional activation and connectivity. We will utilize a modified anticipatory stimulation paradigm as well as an empathy and judging other's pain task, and employ multi-modal magnetic resonance imaging (MRI) methods including event related functional MRI, morphometric MRI, and diffusion tensor imaging to test the hypotheses. We will also explore the association between patients' imaging data and the severity of deficits in the three symptom domains of autism. This innovative approach involving the integration of sensory/perceptual and cognitive tasks, multi-modal neuroimaging, and clinical testing, as well as linking of this project to other ongoing studies that directly investigate VENs at the neuronal level, will provide specific and comprehensive functional and anatomical insight into the neural mechanisms of this disorder, which will enlighten our understanding of autism at both neuronal and cognitive levels and may also guide novel treatment approaches. PUBLIC HEALTH RELEVANCE: Autism is characterized as a qualitative impairment in reciprocal social interaction and communication, with a restricted, repetitive and stereotyped pattern of behavior, interest, and activities, affecting as many as six in a thousand children and adults. Although innumerable landmark advances have been achieved in the medical sciences, our knowledge about pathophysiology of autism is still very limited. This innovative approach involving the integration of sensory/perceptual and cognitive tasks, multi-modal neuroimaging, and clinical testing will provide specific and comprehensive functional and anatomical insight into the neural mechanisms of this disorder and may also guide novel treatment approaches.