Anterior Cingulate and Fronto-Insular Related Brain Networks in Autism

描述（由申请人提供）：自闭症的特征是在互惠的社会互动和沟通方面存在定性障碍，具有限制的、重复的和刻板的行为、兴趣和活动模式。自闭症是一组被称为自闭症谱系障碍（ASDs）的大脑发育障碍中最常见的疾病，包括自闭症、阿斯伯格综合症和没有特别说明的广泛性发育障碍。自闭症影响儿童和成人的比例高达千分之六。尽管医学科学取得了无数里程碑式的进展，但我们对自闭症病理生理学的了解仍然非常有限。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梭形神经元，可能参与对复杂情况的快速和直观评估。这些区域的VENs缺陷可能导致无法在社会环境中处理复杂的、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损害可能与VENs的异常发育有关。我们建议研究ACC-和fi相关的大脑网络在高功能ASD患者中参与低水平感觉和知觉以及高水平认知过程的异常。我们假设，与正常对照相比，ASD患者的ACC和FI在异常功能激活和连接方面存在核心缺陷。我们将利用改进的预期刺激范式以及共情和判断他人疼痛任务，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影像数据与自闭症的三个症状域缺陷的严重程度之间的关系。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研究联系起来，直接在神经元水平上研究VENs，将为这种疾病的神经机制提供具体而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。与公共卫生相关：自闭症的特点是在相互的社会互动和沟通方面出现质的障碍，行为、兴趣和活动模式受到限制、重复和定型，每一千名儿童和成人中就有六名受到影响。尽管医学科学取得了无数里程碑式的进展，但我们对自闭症病理生理学的了解仍然非常有限。这种创新的方法包括感觉/知觉和认知任务的整合，多模态神经成像和临床测试，将为这种疾病的神经机制提供具体和全面的功能和解剖学见解，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.