FRMI OF THE PERSON IDENTITY NETWORK: AGING AND APOE

描述(申请人提供)：个人-身份网络(PIN)是识别和识别熟悉的人的基础，被认为是长期语义记忆系统的领域。对其神经基础的了解，主要来自对脑病患者的研究，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项与事件相关的功能磁共振实验，旨在更好地了解PIN的神经生物学基础、健康老龄化对PIN的影响，以及识别与PIN相关的大脑激活模式，这些模式可能确定阿尔茨海默病(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)识别与获取PIN的不同模式(面孔与名字)相关的共同和独特的神经系统，以及(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(1)对比年轻和老年参与者在姓名和面孔识别方面产生的激活模式，以及(2)比较最近和遥远的名人的激活模式，来检查远程记忆中可能存在的时间梯度的神经基础，来检验健康老龄化和低遗传风险对从PIN中提取的影响。在目标3中，PIN的神经表现将在老年健康参与者中进行检测，这些参与者具有发展为AD的遗传易感性，原因是他们与AD有兄弟姐妹，并且至少拥有一个载脂蛋白E e4(APOE E4)等位基因。将在两个PIN实验中检验阿尔茨海默病风险的神经意义，这两个实验涉及：(1)著名的面孔/名字识别，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有关，该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接受第二次神经成像研究，以评估与PIN相关的大脑激活模式作为AD高危状态的功能的纵向变化。该项目的结果有望为我们理解调节从PIN取回的神经系统以及可能预示年龄相关记忆功能异常的记忆病理的神经生物学基础提供新的见解。

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.