Relational Memory and Aging: Role of Prefrontal Lobe

描述（由申请人提供）： 虽然中风和创伤性脑损伤只影响一小部分人，但如果我们活得足够长，有一种脑功能障碍会影响我们所有人-正常衰老。随着年龄的增长，我们大脑的解剖和功能完整性会下降，我们的认知能力也会下降。即使相对温和，这种下降也影响到大量人口。任何合理的治疗方法的发展都取决于对衰老对认知神经基础的影响的清晰理解。在人类中，这些影响可以使用功能性神经成像技术来揭示，例如功能性MRI（fMRI），它可以直接将与年龄相关的认知缺陷与大脑活动的变化联系起来。 受衰老影响最大的认知功能之一是关系记忆。老年人在关系记忆（RM）上的记忆缺陷是项目记忆（IM）的两倍。IM指的是记住过去发生的事情，RM指的是记住相关的信息，如地点、时间和方式。据了解，RM是更依赖于内侧颞叶（MTL）和前额叶皮层（PFC）比IM，但不同的MTL和PFC区域的不同形式的RM的贡献是不清楚的。也不确定这些贡献如何随着老龄化而变化。此外，调节衰老对RM影响的关键因素的神经基础，如预先存在的知识和干扰的作用，在很大程度上是未知的。我们建议进行五项fMRI研究来解决这些问题。 具体而言，我们有四个具体的目标：（1）比较年轻人和老年人不同形式的RM的神经相关性。研究1将比较特征、空间和时间顺序RM，研究2将比较特征和语义RM，研究3将比较相似与不同类型刺激之间的关联;（2）揭示影响年轻人和老年人语义RM的因素的神经相关性。研究4将探讨预先存在的语义联想的作用，研究5，前摄干扰的作用;（3）阐明年轻人和老年人RM编码和提取的神经相关性。为了实现这一目标，所有五个fMRI研究提出将比较编码和提取活动直接在受试者;（4）调查PFC和MTL之间的相互作用，在年轻和老年人RM。脑卒中相关的RM缺陷可能反映了PFC和MTL区域之间的断开。为了研究这个问题，我们将RM性能的年龄相关变化与PFC-MTL连接的变化联系起来，包括功能（活动相关性）和解剖学（用弥散张量成像测量的白质完整性）。总之，这些研究的结果将澄清与年龄相关的缺陷在RM的神经相关性，并将有重要的意义，促进健康。

DESCRIPTION (provided by applicant): Whereas stroke and traumatic brain injury affect only a fraction of the population, there is a type of brain dysfunction that will affect us all if we live long enough---normal aging. As we age, the anatomical and functional integrity of our brain declines as do our cognitive abilities. Even if relatively mild, this decline impacts a large number of the population. The development of any rational remedial approach depends on a clear understanding of the effects of aging on the neural basis of cognition. In humans these effects can be revealed using functional neuroimaging techniques such as functional MRI (fMRI), which can directly link age-related cognitive deficits to changes in brain activity. One of the cognitive functions most affected by aging is relational memory. Older adults' memory deficits are twice as large on relational memory (RM) than on item memory (IM). Whereas IM refers to remembering what happened in the past, RM refers to remembering the associated information of where, when, and how. It is known that RM is more dependent on the medial temporal lobes (MTL) and the prefrontal cortex (PFC) than IM, but the contributions of various MTL and PFC regions to different forms of RM are unclear. It is also uncertain how these contributions change as a function of aging. Moreover, the neural bases of critical factors modulating the effects of aging on RM, such as the role of pre-existent knowledge and interference, are largely unknown. We propose to conduct five fMRI studies to address these issues. In particular, we have four specific aims: (1) Compare the neural correlates of different forms of RM in younger and older adults. Study 1 will compare featural, spatial, and temporal-order RM, Study 2 will compare featural and semantic RM, and Study 3 will compare associations between similar vs. different kinds of stimuli; (2) Reveal the neural correlates of factors affecting semantic RM in younger and older adults. Study 4 will investigate the role of pre-existent semantic associations and Study 5, the role of proactive interference; (3) Clarify the neural correlates of RM encoding and retrieval in younger and older adults. To accomplish this aim, all five fMRI studies proposed will compare encoding and retrieval activity directly within-subjects; (4) Investigate the interaction between PFC and MTL during RM in younger and older adults. Age-related RM deficits may reflect a disconnection between PFC and MTL regions. To investigate this issue, we will relate age-related changes in RM performance to changes in PFC-MTL connectivity, both in terms of function (correlation in activity) and anatomy (white-matter integrity measured with diffusion tensor imaging). Taken together, the results of these studies will clarify the neural correlates of age-related deficits in RM and will have important implications for the promotion of health.