NEUROANATOMICAL/NEUROCHEMICAL REORGANIZATION AFTER EARLY INSULT LIMBIC CIRCUIT

早期损伤边缘回路后的神经解剖学/神经化学重组

• 批准号: 6108886
• 负责人: Daniel Jay Felleman
• 金额: $ 16.82万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108886
• 关键词: NEUROANATOMICAL; NEUROCHEMICAL; REORGANIZATION; AFTER; EARLY

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.

自闭症等发育障碍提供了独特的机会 识别重要的大脑结构和功能回路 是复杂、知觉、认知和社会行为的基础。这 提议的多学科计划，利用行为测试 （项目 I）和自闭症儿童的 MRI 光谱学（项目 II），以及 猴子的行为、MRI 光谱和神经解剖学研究 （项目 II 和 III），提供了可测试的全面分析 人类自闭症动物模型。根据这一假设，早期损伤 杏仁核-眶额回路会导致发育障碍 以社交、情感和认知障碍为特征 行为。项目 IV 将评估婴儿的程度 对眶额-杏仁核回路损伤做出反应。为了 充分评估功能重组的可能机制 在这种新生儿脑损伤之后，正常婴儿和正常成人 皮质边缘连接的模式将使用现代评估 神经解剖通路追踪技术。这些图案的 然后将连接与免疫细胞化学相关联 该电路的发展和密切相关的结构。接下来， 成人皮质-边缘连接模式的评估 杏仁核受到早期或晚期损伤的猴子 眶额皮质。这些结果将确定 发育中的神经系统可以利用补偿机制 稳定发育短暂的神经通路，招募新的 弱关联结构之间的通路，或招募新的目标 结构进入功能性皮质边缘回路。总体而言，这 研究将为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。