Associative learning and brain structure in individuals at risk for dementia

描述（由申请人提供）：本申请指导患者导向研究职业发展奖（K23）旨在为候选人提供认知神经科学互补和整合领域的特定技能和指导，为独立研究职业做准备。该提案描述了一个全面的五年培训计划，重点是在以下三个领域扩展候选人的技能和发展专业知识：(1)衰老和痴呆风险神经心理学的理论和应用方面；(2)以扩散张量成像（DTI）为重点的结构成像方法；(3)将这两个领域与实验学习范式——眨眼经典条件反射（EBCC）相结合，以更好地理解大脑结构-功能关系的本质。本建议和培训计划的重点在于每一种方法的力量和通过它们的整合所获得的协同作用。这将通过先进的培训、指导、教学和在这些内容领域的正式指导来完成，在丰富的培训环境中，由熟练和敬业的导师、顾问和顾问团队组成。培训环境将为候选人提供优秀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各方面的专家，并将确保模范指导。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来将阿尔茨海默病（AD）和脑血管疾病（CVD）风险的老年人群的行为变化与潜在的神经病理变化联系起来。AD和CVD对大脑不同区域产生不利影响，具有不同的神经解剖学和神经心理学基础。这些脑区与EBCC联合反应的获得和表达相关的回路有关。该研究有三个具体目的：(1)确定在复杂的EBCC学习任务中的表现是否可以将AD风险个体与CVD分离开来；(2)确定这些学习障碍是否与可分离的形态变化有关；(3)纵向检查下降率。

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. PUBLIC HEALTH RELEVANCE: Evidence suggests that cognitive disorders that are increasingly prevalent with age have their beginnings in physiological, anatomical, and cognitive alterations that are in place years before a clinical entity is detected. This project will determine if EBCC can detect behavioral changes in individuals at risk for dementia before those diseases develop, and provide unique information on brain structure-function relationships.