Adolescent Working Memory and White Matter Development

描述(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，特别是在额叶，与包括工作记忆能力在内的几个高级认知功能领域的改善不谋而合。已有文献证明，工作记忆技能对其他几个认知领域的完整表现至关重要。在青春期出现的一系列神经和精神疾病中，已经证明了工作记忆的缺陷。然而，即使在正常发育的青少年中，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，以更清楚地探索额叶白质发育，因为它与90名典型发育中的青少年(12至17岁)的语言和空间工作记忆功能有关。假设1)工作记忆能力与年龄呈正相关，2)青少年在言语和空间工作记忆任务中表现出大脑半球的分离，并随着年龄的增长而变得更加明显，3)前额叶白质完整性与年龄呈显著正相关，并将中介年龄与工作记忆成绩之间的正相关，4)前额叶白质完整性与工作记忆任务中邻近皮质的fMRI反应呈正相关。申请人申请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、功能磁共振方面的专门知识发展、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与儿童和青少年进行科学研究的道德方面的持续培训。拟议的培训计划将包括有组织的课程作业、研讨会以及由开发和神经成像领域的专家进行指导。总之，这项培训和研究计划的实施将为了解青春期工作记忆的神经生物学基础提供一个亟需的框架的开端，并使申请者能够过渡到专门从事青少年认知和神经发育纵向检查的独立调查者。

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.