Associative learning and brain structure in individuals at risk for dementia

描述（由申请人提供）：本申请辅导以患者为导向的研究职业发展奖（K23）旨在为候选人在认知神经科学的补充和综合领域提供特定的技能和指导，为独立的研究生涯做准备。本建议书描述了一个全面的五年培训计划，重点是扩大候选人的技能和发展以下三个领域的专门知识：（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）这两个领域与实验学习范式的整合，眨眼经典条件反射（EBCC），以更好地了解大脑结构-功能关系的性质。本建议和培训计划的重点在于每种方法的优势以及通过整合所获得的协同作用。这将通过高级培训，指导，教学法和这些内容领域的正式指导来实现，并在一个丰富的培训环境中与熟练和专业的导师，顾问和顾问团队合作。培训环境将为候选人提供出色的机构支持和巨大的资源。导师、顾问和咨询人包括拟议培训和研究领域各个方面的专家，并将确保提供示范性指导。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，将行为变化与阿尔茨海默病（AD）和脑血管疾病（CVD）风险人群中的潜在神经病理学变化联系起来。AD和CVD在不同区域对大脑产生不利影响，其特征在于不同的神经解剖学和神经心理学基础。这些脑区与EBCC关联反应的获得和表达相关的回路有关。该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风险个体与CVD分离，（2）确定这些学习障碍是否与可分离的形态学变化相关，以及（3）纵向检查下降率。 公共卫生相关性：有证据表明，随着年龄的增长越来越普遍的认知障碍在生理，解剖和认知改变中开始，这些改变在临床实体被检测到之前几年就已经存在。该项目将确定EBCC是否可以在这些疾病发展之前检测出有痴呆风险的个体的行为变化，并提供有关大脑结构-功能关系的独特信息。

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.