Neurophysiology of Prefrontal Cortical Development

描述(申请人提供)：与其他脊椎动物相比，灵长类动物前额叶皮质的大小急剧增加，其进化扩展反映了这些物种注意力、记忆和执行功能的发展。在发育过程中，前额叶皮质经历了一个漫长的成熟过程，从青春期一直延伸到成年早期。许多精神疾病的发病与前额叶皮质的成熟有关，最明显的是精神分裂症，它在成年早期就表现出来了。冲动控制在成年后也会改善，发育不充分与犯罪、药物滥用和其他对健康和社会有重要意义的条件有关。人们对前额叶皮质在青春期和成年期早期所经历的生理变化知之甚少，以调节认知控制力的增强。利用最近的方法和概念上的进展，我们建议研究青春期后发生的前额叶皮质生理学和功能连接的变化。我们建议使用非人类灵长类动物模型，这将允许我们在幼年和成年动物的前额叶皮质进行神经生理学记录。我们的研究还将采样后顶叶皮质，这是一个与前额叶皮质相互连接的区域。这将作为一个控制区，使我们能够确定前额叶皮质成熟的独特之处，也将使我们能够研究前额叶皮质和后顶叶皮质之间功能连接的变化。我们的研究将利用经过训练的猴子来执行需要注意、工作记忆和执行控制的行为任务。这些实验将提供关于前额叶皮质发育如何改变其生理反应的见解，这对于理解和治疗与前额叶皮质成熟问题相关的精神疾病至关重要。 与公共健康相关：这项拟议的研究将确定前额叶皮质神经元在青春期和成年期之间的功能变化。从这些实验中获得的知识将阐明注意力和记忆等高级认知过程的发展，这对于了解注意力缺陷障碍等疾病和精神分裂症等精神疾病的生物学基础是必要的。

DESCRIPTION (provided by applicant): The size of the prefrontal cortex has increased dramatically in primates compared to other vertebrates and its evolutionary expansion mirrors the development of attention, memory, and executive function in these species. Developmentally, the prefrontal cortex undergoes a long maturation process that extends through puberty and into early adulthood. A number of mental illnesses have onsets linked to the maturation of the prefrontal cortex, most notably schizophrenia, which manifests itself in early adulthood. Impulse control also improves in adulthood, and failure to develop adequately is associated with delinquency, drug abuse, and other conditions of health and social significance. Little is known about the physiological changes that the prefrontal cortex undergoes during puberty and early adulthood so as to mediate increased cognitive control. Taking advantage of recent methodological and conceptual advances, we propose to investigate the changes of prefrontal cortical physiology and functional connectivity that occur after puberty. We propose to use a non-human primate model which will allow us to conduct neurophysiological recordings in the prefrontal cortex of juvenile and adult animals. Our studies will also sample the posterior parietal cortex, an area interconnected with the prefrontal cortex. This will serve as a control area allowing us to determine what is unique about the maturation of the prefrontal cortex, and it will also allow us to study changes of functional connectivity between the prefrontal cortex and posterior parietal cortex. Our study will make use of monkeys trained to perform behavioral tasks that require attention, working memory, and executive control. These experiments will offer insights on how development of the prefrontal cortex alters its physiological responses which will be essential for understanding and treating mental illnesses associated with problems of prefrontal cortical maturation. PUBLIC HEALTH RELEVANCE: The proposed research will determine how the functions of prefrontal cortex neurons change between adolescence and adulthood. Knowledge drawn from these experiments will elucidate the development of higher cognitive processes such as attention and memory, which is necessary for understanding the biological basis of conditions such as Attention Deficit Disorder and mental illnesses such as schizophrenia.