FRMI OF THE PERSON IDENTITY NETWORK: AGING AND APOE

描述（由申请人提供）：个人身份网络（PIN），这是识别和识别熟悉的人的基础，被认为是在长期语义记忆系统的领域。其神经基础的知识，主要来自脑损伤患者的研究，表明PIN可能有重要的和独特的功能相比，一般的对象语义系统。这项为期五年的提案包括七个与事件相关的功能性MRI实验，旨在更好地了解PIN的神经生物学基质，健康老龄化对PIN的影响，以及识别PIN相关的大脑激活模式，这些模式可以识别有发展阿尔茨海默病（AD）风险的个体中异常的最早阶段。在目标1中，在健康的年轻参与者中进行了两项实验：（1）识别与PIN的不同访问模式（面孔与姓名）相关的共同和独特的神经系统，以及（2）将PIN的检索与其他语义类别（熟悉的地标）的检索进行比较。在目标2中，我们将通过以下方式研究健康老龄化和发展AD的低遗传风险对从PIN提取的影响：（1）对比年轻和老年参与者产生的姓名和面部识别的激活模式，以及（2）比较最近和遥远的名人的激活模式，以检查远程记忆中可能的时间梯度的神经基质。在目标3中，将在老年健康受试者中检查PIN的神经表征，这些受试者由于具有患有AD的兄弟姐妹并且具有至少一个载脂蛋白E e4（APOE e4）等位基因而具有发展AD的遗传易感性。将在两个PIN实验中检查处于发展AD的风险中的神经意义，所述两个PIN实验涉及：（1）著名的面部/姓名识别，和（2）时间梯度。这些PIN研究将确定APOE e4等位基因的存在是否与一种独特的激活模式相关，这种激活模式可能作为随后认知能力下降的早期标志。在目标4中，老年参与者将在三年后进行第二次神经影像学研究，以评估与PIN相关的大脑激活模式的纵向变化，作为AD风险状态的函数。该项目的结果预计将提供新的见解，我们的理解的神经系统，介导检索从PIN，和记忆病理的神经生物学基板，可能预示着异常的年龄相关的记忆功能。

DESCRIPTION (provided by applicant): The person-identity network (PIN), which underlies the recognition and identification of familiar people, is considered within the domain of the long-term semantic memory system. Knowledge of its neural underpinnings, derived primarily from studies of brain-lesioned patients, suggest that the PIN may have important and unique features in comparison to the general object semantic system. This five-year proposal consists of seven event-related functional MRI experiments designed to better understand the neurobiological substrates of the PIN, effects of healthy aging on the PIN, and the identification of PIN-related brain activation patterns that may identify the earliest stages of abnormality in individuals at-risk for developing Alzheimer's disease (AD). In Aim 1, two experiments in healthy young participants will: (1) identify common and unique neural systems associated with distinct modes of access (faces versus names) to the PIN, and (2) compare retrieval from the PIN with retrieval from other semantic categories (familiar landmarks). In Aim 2, we will examine the effect of healthy aging and low genetic risk for developing AD on retrieval from the PIN by: (1) contrasting activation patterns produced by younger and older participants for name and face recognition, and (2) comparing activation patterns for recent and remote famous people to examine the neural substrates of a possible temporal gradient in remote memory. In Aim 3, the neural representation of the PIN will be examined in older healthy participants with a genetic susceptibility toward developing AD by virtue of having a sibling with AD and possessing at least one apolipoprotein E e4 (APOE e4) allele. The neural significance of being at-risk for developing AD will be examined in two PIN experiments involving: (1) famous face/name recognition, and (2) temporal gradient. These PIN studies will determine whether the presence of the APOE e4 allele is associated with a unique activation pattern that may serve as an early marker for subsequent cognitive decline. In Aim 4, older participants will undergo a second neuroimaging study after three years to assess longitudinal changes in brain activation patterns associated with the PIN as a function of AD at-risk status. Results of this project are expected to provide novel insights into our understanding of the neural systems that mediate retrieval from the PIN, and the neurobiological substrates of memory pathology that may presage abnormal age-related memory functioning.