Prefrontally-mediated memory in phenylketonuria

苯丙酮尿症中前额介导的记忆

• 批准号: 6873692
• 负责人: Desiree A White
• 金额: $ 29.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873692
• 关键词: adolescence (12-20); aging; behavioral /social science research tag; blood tests; brain morphology; child psychology; clinical research; dopamine; human subject; learning; long term memory; longitudinal human study; magnetic resonance imaging; memory; middle childhood (6-11); neural information processing; neuropathology; neurotransmitter metabolism; patient oriented research; phenylalanine; phenylketonurias; prefrontal lobe /cortex; psychological tests; short term memory; tyrosine

DESCRIPTION (provided by investigator): Recent work from our research group shows that school-age children with phenylketonuria (PKU) exhibit impairments in two prefrontally-mediated cognitive abilities of crucial importance to early learning: working memory and strategic processing in long-term memory. These impairments are more evident in older than younger children, suggesting that the impairments are not stable across development but instead may emerge with age. In the proposed research, the developmental trajectory of working memory and strategic memory processing will be charted longitudinally to determine if impairments emerge in individual children. Two neuropathological mechanisms that may underlie impairments in prefrontally-mediated aspects of memory also will be examined. This research has implications for the development of rehabilitation strategies designed to improve learning and memory in children with PKU and other developmental disorders affecting prefrontal function. The aims and the methods for addressing the aims of this study are as follows: (1) To test the hypothesis that children with PKU exhibit impairments in prefrontally-mediated aspects of memory. To achieve this aim, working memory and strategic memory processing tasks will be administered to children with PKU who range from 7 to 18 years of age. Comparisons will be made with demographically matched, typically developing children. (2) To test the hypothesis that impairments in prefrontally-mediated aspects of memory emerge as children with PKU age. To achieve this aim, working memory and strategic memory processing will be evaluated on a longitudinal basis. By doing so, the developmental trajectory of prefrontally-mediated aspects of memory will be defined at the level of individual children. (3) To test the hypothesis that white matter abnormalities contribute to impairments in prefrontally-mediated aspects of memory in children with early-treated PKU. This aim will be achieved through the use of diffusion tensor imaging (DTI), a neuroimaging technique permitting refined examination of white matter integrity. Dopamine deficiency also will be examined by assessing blood phenylalanine (a dopamine precursor) levels. Findings from DTI and phenylalanine levels will be examined in relation to findings from the memory tasks.

描述（由研究人员提供）：我们研究小组的最新工作表明，患有苯酮尿症（PKU）的学龄儿童在两种前额叶介导的认知能力中表现出损害，这对早期学习至关重要：长期记忆中的工作记忆和战略处理。这些障碍在年龄较大的孩子中更为明显，这表明这些障碍在整个发展过程中不稳定，而是随着年龄的增长而出现。在拟议的研究中，将纵向绘制工作记忆和战略记忆处理的发展轨迹，以确定个别儿童的障碍是否出现。还将检查两种可能构成记忆前介质方面损害的神经病理机制。这项研究对旨在改善PKU​​儿童和其他影响前额叶功能的儿童的学习和记忆的康复策略的发展具有影响。解决这项研究目的的目的和方法如下：（1）检验以下假设：PKU儿童在记忆的前介质介导的方面表现出障碍。为了实现这一目标，将向患有7至18岁范围内的PKU儿童进行工作记忆和战略记忆处理任务。比较将与人口匹配的，通常是发展的儿童进行比较。 （2）检验以下假设：随着PKU年龄的儿童，出现了记忆前介质方面的损害。为了实现这一目标，将在纵向上评估工作记忆和战略记忆处理。通过这样做，将在单个孩子的水平上定义记忆前介导的方面的发展轨迹。 （3）检验以下假设：白质异常有助于早期治疗PKU儿童的记忆前介导的障碍。通过使用扩散张量成像（DTI），这是一种神经影像学技术，允许对白质完整性进行完善的检查来实现此目标。还将通过评估血液苯丙氨酸（多巴胺前体）水平来检查多巴胺缺乏症。 DTI和苯丙氨酸水平的发现将与内存任务的发现有关。