Anterior Cingulate and Fronto-Insular Related Brain Networks in Autism

描述(申请人提供)：自闭症的特征是在相互的社会交往和交流中的一种质的损害，具有受限的、重复的和刻板印象的行为、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、阿斯伯格综合征和未另行指定的普及性发育障碍。自闭症影响多达千分之六的儿童和成年人。虽然医学科学已经取得了无数里程碑式的进展，但我们对自闭症的病理生理学的了解仍然非常有限。Von Economo神经元(Vens)是一种大的、双极、纺锤形神经元，在人的前扣带回皮质(ACC)和额岛皮质(FI)中含量最高，可能参与对复杂情况的快速和直观评估。这些区域的VEN的缺陷可能导致无法在社会环境中处理复杂、不可预测和新奇的信息。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VEN的异常发育有关。我们建议在高功能ASD患者中调查涉及低水平感觉和知觉以及高水平认知过程的ACC和FI相关脑网络的异常。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将存在核心缺陷。我们将利用改进的预期刺激范式以及移情和判断他人疼痛的任务，并使用包括事件相关功能磁共振成像、形态测量磁共振成像和扩散张量成像在内的多模式磁共振成像(MRI)方法来检验假设。我们还将探索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联系。这一创新的方法包括整合感觉/知觉和认知任务、多模式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在神经元水平上研究Ven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，并可能指导新的治疗方法。与公共卫生相关：自闭症的特征是在互惠的社会互动和交流中出现质的损害，行为、兴趣和活动具有受限、重复和刻板印象的模式，影响多达千分之六的儿童和成年人。虽然医学科学已经取得了无数里程碑式的进展，但我们对自闭症的病理生理学的了解仍然非常有限。这一创新的方法涉及到感觉/知觉和认知任务的整合、多模式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，并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.