Associative learning and brain structure in individuals at risk for dementia

描述(由申请者提供)：本申请书旨在为申请人提供认知神经科学互补和综合领域的特定技能和指导，为独立的研究生涯做准备。这项建议描述了一个全面的五年培训计划，集中在以下三个领域扩大候选人的技能和发展专门知识：(1)衰老和痴呆风险的神经心理学的理论和应用方面，(2)结构成像方法，重点是扩散张量成像(DTI)，以及(3)将这两个领域与实验性学习范式--眨眼经典条件反射(EBCC)相结合，以更好地了解大脑结构-功能关系的本质。这项提议和培训计划的重点在于每种方法的长处以及通过将其整合而产生的协同作用。这将通过这些内容领域的高级培训、指导、教学和正式指导来实现，在丰富的培训环境中，将有一支技术娴熟、敬业的导师、顾问和顾问团队。培训环境将为候选人提供良好的制度支持和巨大的资源。导师、顾问和顾问包括拟议培训和研究领域的各个方面的专家，并将确保提供模范指导。拟议的研究项目将使用眨眼经典条件反射范式和神经心理学评估，将阿尔茨海默病(AD)和脑血管疾病(CVD)风险人群的行为变化与潜在的神经病理变化联系起来。AD和CVD在不同的区域对大脑产生不利影响，并具有不同的神经解剖学和神经心理学基础。这些脑区参与了EBCC关联反应的获得和表达。这项建议有三个具体目标：(1)确定在复杂的EBCC学习任务中的表现是否可以将AD高危个体与CVD分离，(2)确定这些学习障碍是否与可分离的形态计量学变化有关，以及(3)纵向检查递减率。

DESCRIPTION (provided by applicant): This application for a Mentored Patient-Oriented Research Career Development Award (K23) is intended to provide specific skills and mentorship to the candidate in complementary and integrative areas of cognitive neuroscience in preparation for an independent research career. This proposal describes a comprehensive five- year training plan focused on expanding the candidate's skills and developing expertise in the following three areas: (1) theoretical and applied aspects of the neuropsychology of aging and dementia risk, (2) structural imaging methodologies with an emphasis on diffusion tensor imaging (DTI), and (3) the integration of these two areas with an experimental learning paradigm, eyeblink classical conditioning (EBCC), to better understand the nature of brain structure-function relationships. The focus of this proposal and training plan lies in the strength of each approach and the synergy gained through their integration. This will be accomplished with advanced training, mentorship, didactics, and formal instruction in these content areas in an enriched training environment with a team of skilled and dedicated mentors, consultants, and advisors. The training environments will provide excellent institutional support and tremendous resources to the candidate. The mentors, advisors, and consultants include experts in each facet of proposed training and research areas and will ensure exemplary guidance. The proposed research project will use the eyeblink classical conditioning paradigm and neuropsychological assessment to link behavioral changes to underlying neuropathological changes in a population of aging individuals at risk for Alzheimer's disease (AD) and cerebrovascular disease (CVD). AD and CVD adversely impact the brain in different regions and are characterized by distinct neuroanatomical and neuropsychological underpinnings. These brain regions have been implicated in the circuit underlying the acquisition and expression of EBCC associative responses. This proposal has three specific aims: (1) to determine if performance in a complex EBCC learning task can dissociate individuals at risk AD from CVD, (2) to determine if these learning impairments will be associated with dissociable morphometric changes, and (3) to examine the rates of decline longitudinally.