NEUROANATOMICAL/NEUROCHEMICAL REORGANIZATION AFTER EARLY INSULT LIMBIC CIRCUIT

自闭症等发育障碍提供了一个独特的机会 确定重要的大脑结构和功能回路 复杂的、感性的、认知的和社会的行为是其基础。这个 建议的多学科计划，利用行为测试 (项目I)和自闭症儿童的核磁共振波谱(项目II)，以及 猕猴的行为学、核磁共振波谱和神经解剖学研究 (项目II和III)，提供了对可测试的全面分析 人类自闭症的动物模型。根据这一假设，早期损伤 杏仁核-眶前叶环路导致发育障碍 以社交、情感和认知方面的混乱为特征的 行为。项目IV将评估婴儿在何种程度上 对眼眶额叶-杏仁核环路的损伤做出反应。为了 充分评估职能重组的可能机制 在这种新生儿脑损伤之后，正常婴儿和正常成年人 皮质-边缘连接的模式将使用现代 神经解剖路径追踪技术。这些模式 然后，连接将与免疫细胞化学相关 这一电路的发展和密切相关的结构。接下来， 成人皮质-边缘连接类型的评估 接受杏仁核早期或晚期损伤的猴子或 眶前叶皮质。这些结果将在多大程度上确立 发育中的神经系统可以利用代偿机制 稳定发育暂时性神经通路，招募新的 弱关联结构之间的路径，或招募新目标 结构转化为功能性皮质-边缘环路。总体而言，这 研究将对我们的理解做出重大贡献 广泛性发育障碍的神经生物学基础。

Developmental disorders such as autism offer a unique opportunity to identify important brain structures and functional circuits that underlie complex, perceptual, cognitive, and social behaviors. The proposed multi-disciplinary program, utilizing behavioral testing (Project I) and MRI spectroscopy in autistic children (Project II), and behavioral, MRI-spectroscopic, and neuroanatomical studies in monkeys (Projects II and III), offers a comprehensive analysis of testable animal model of human autism. According to this hypothesis, early damage to the amygdala-orbitofrontal circuit causes a developmental impairment characterized by disturbances in social, emotional, and cognitive behavior. Project IV will evaluate the degree to which the infant responds to injury to the orbitofrontal-amygdala circuit. In order to evaluate fully the possible mechanisms of functional reorganization following this neonatal brain damage, the normal infant and normal adult patterns of cortico-limbic connections will be evaluated using modern neuroanatomical pathways tracing techniques. These patterns of connections will then be correlated with the immunocytochemical development of this circuit and closely related structures. Next, the patterns of cortico-limbic connections with be evaluated in adult monkeys that received either early or late lesions of the amygdala or orbitofrontal cortex. These results will establish the degree to which the developing nervous system can utilize compensatory mechanisms to stabilize developmentally transient neural pathways, to recruit new pathways between weakly associated structures, or to recruit new target structures into functional cortico-limbic circuits. Overall, this research will make a significant contribution towards our understanding of the neurobiological bases of pervasive developmental disorders.