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: 6442982
• 负责人: Daniel Jay Felleman
• 金额: $ 16.41万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442982
• 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一个独特的机会， 识别重要的大脑结构和功能回路， 构成了复杂的、知觉的、认知的和社会行为的基础。的 建议多学科计划，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 猴的行为、MRI光谱和神经解剖学研究 （项目二和三），提供了一个全面的分析， 人类自闭症的动物模型根据这一假设， 杏仁核-眶额神经回路会导致发育障碍 以社交、情感和认知障碍为特征 行为项目四将评估婴儿 对眶额杏仁核回路的损伤有反应为了 充分评估职能重组的可能机制 在新生儿脑损伤后，正常婴儿和正常成人 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 连接将与免疫细胞化学 这条线路的发展和密切相关的结构。接下来 成人皮质-边缘系统连接的模式 接受早期或晚期杏仁核损伤的猴子， 眶额皮质这些结果将确定 发育中的神经系统可以利用代偿机制 稳定发育中短暂的神经通路， 弱相关结构之间的通路，或招募新的靶点 结构转化为功能性皮质边缘回路。总体而言，这 研究将对我们理解 广泛性发育障碍的神经生物学基础