Adolescent Working Memory and White Matter Development

描述（由申请人提供）：利用现代神经成像技术的研究提供了明确的证据，表明青少年的大脑正在积极发育。这种神经发育，特别是额叶的神经发育，与包括工作记忆能力在内的高级认知功能的几个领域的改善相吻合。工作记忆技能对其他几个认知领域的完整表现至关重要。在青春期出现的一些神经和精神疾病中，已经证明了工作记忆的缺陷。然而，即使是正常发育的青少年，工作记忆的神经生物学基础仍然不清楚。目前的横断面研究建议整合神经心理学，功能磁共振成像（fMRI）和扩散张量成像（DTI）技术，以更清楚地探讨额叶白色物质的发展，因为它涉及到两个语言和空间工作记忆功能在90个典型的青少年（年龄12至17岁）。假设1）工作记忆能力与年龄正相关，2）青少年在言语和空间工作记忆任务之间表现出半球分离，并且随着年龄的增长而变得更加明显，3）前额叶白色物质完整性与年龄呈显著正相关，并将介导年龄与工作记忆表现之间的正相关，（4）在工作记忆任务中，前额叶白色物质的完整性与邻近皮层的fMRI反应呈正相关。申请人正在申请一个为期五年的指导职业发展奖（K08），以发展回答这些研究问题所需的技能和专业知识。职业发展活动将包括DTI数据收集和分析方面的培训，fMRI专业知识的发展，以发展为重点的纵向研究设计和分析技术方面的培训，以及儿童和青少年科学研究道德行为方面的继续培训。拟议的培训计划将包括结构化的课程、研讨会以及发育和神经成像领域专家的指导。总之，这个培训和研究计划的实施将提供一个急需的框架，了解工作记忆在青春期的神经生物学基板的开始，并将允许申请人过渡到一个独立的研究者，专门从事青少年认知和神经发育的纵向检查。

DESCRIPTION (provided by applicant): Studies utilizing modern neuroimaging techniques have provided clear evidence that the adolescent brain is actively developing. This neurodevelopment, particularly in the frontal lobes, coincides with improvements in several areas of higher order cognitive functioning, including working memory abilities. It has been documented that working memory skills are crucial to the intact performance in several other cognitive domains. Deficits in working memory have been demonstrated among a number of neurological and psychiatric conditions that manifest during adolescence. However, the neurobiological substrates of working memory in even normally developing adolescents remain unclear. The current cross-sectional study proposes to integrate neuropsychological, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques to more clearly explore frontal lobe white matter development as it relates to both verbal and spatial working memory functioning in 90 typically developing adolescents (ages 12 to 17). It is hypothesized that 1) working memory abilities will be positively associated with age, 2) adolescents will show a hemispheric dissociation between the verbal and spatial working memory tasks that will become more pronounced with increasing age, 3) prefrontal white matter integrity will show a significant positive correlation with age and will mediate the positive relationship between age and working memory performance, and 4) prefrontal white matter integrity will be positively associated with nearby cortical fMRI response during the working memory tasks. The applicant is requesting a five-year mentored Career Development Award (K08) in order to develop the skills and expertise necessary for answering these research questions. Career development activities will include training in DTI data collection and analysis, development of expertise in fMRI, training in developmentally-focused longitudinal study design and analytical techniques and continued training in the ethical conduct of scientific research with children and adolescents. The proposed training plan will include structured coursework, seminars, and mentoring by experts in the fields of development and neuroimaging. Together, the implementation of this training and research plan will provide the beginnings of a much-needed framework for understanding the neurobiological substrates of working memory during adolescence and will allow the applicant to transition into an independent investigator specializing in longitudinal examination of adolescent cognition and neurodevelopment.