FRMI OF THE PERSON IDENTITY NETWORK: AGING AND APOE

描述（由申请人提供）：个人身份网络（PIN）是长期语义记忆系统的一个领域，它是识别和识别熟悉的人的基础。对其神经基础的了解主要来源于对脑损伤患者的研究，表明与一般的对象语义系统相比，PIN可能具有重要而独特的特征。这项为期五年的计划包括七个事件相关的功能性MRI实验，旨在更好地了解PIN的神经生物学基础，健康衰老对PIN的影响，以及PIN相关的大脑激活模式的识别，这些模式可能会识别阿尔茨海默病（AD）高危个体的早期异常阶段。在目标1中，在健康的年轻参与者中进行的两个实验将：(1)识别与不同访问模式（面孔与姓名）相关的常见和独特的神经系统，(2)比较从PIN检索与从其他语义类别（熟悉的地标）检索。在目标2中，我们将通过以下方式来研究健康衰老和低遗传风险对AD的影响：(1)对比年轻和年长参与者对姓名和面部识别产生的激活模式，以及(2)比较最近和遥远的名人的激活模式，以研究遥远记忆中可能的时间梯度的神经基础。在Aim 3中，PIN的神经表征将在具有阿尔茨海默病遗传易感性的老年健康参与者中进行检查，这些参与者的兄弟姐妹患有阿尔茨海默病，并且拥有至少一个载脂蛋白e4 （APOE e4）等位基因。我们将通过两个PIN实验来研究AD风险的神经意义，包括：(1)著名的面孔/名字识别，以及(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有关，这种模式可能作为随后认知能力下降的早期标志。在Aim 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风险状态的功能。该项目的结果有望为我们对介导PIN检索的神经系统以及可能预示异常年龄相关记忆功能的记忆病理的神经生物学基础的理解提供新的见解。

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.