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，有一种类型的大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，这种下降也会影响到大量人口。任何合理的补救方法的发展都依赖于对衰老对认知的神经基础的影响的清楚理解。在人类身上，这些效应可以通过功能核磁共振(FMRI)等功能神经成像技术来揭示，这种技术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。 受年龄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)上的记忆缺陷是在项目记忆(IM)上的两倍。IM指的是记住过去发生的事情，而RM指的是记住地点、时间和方式的相关信息。众所周知，与IM相比，RM更依赖内侧颞叶(MTL)和前额叶(PFC)，但不同MTL和PFC区域对不同形式RM的作用尚不清楚。同样不确定的是，这些贡献是如何随着年龄的增长而变化的。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。我们建议进行五项功能磁共振研究来解决这些问题。 具体地说，我们有四个具体目标：(1)比较不同形式的RM在年轻人和老年人中的神经相关性。研究1将比较特征、空间和时间顺序RM，研究2将比较特征RM和语义RM，研究3将比较相似和不同类型刺激之间的联系；(2)揭示影响年轻人和老年人语义RM的因素的神经关联。研究4将考察预先存在的语义联系的作用，研究5，主动干预的作用；(3)阐明在年轻人和老年人中RM编码和提取的神经关联。为了实现这一目标，提出的所有五项功能磁共振研究将直接比较受试者内部的编码和提取活动；(4)调查年轻人和老年人在RM过程中PFC和MTL之间的相互作用。年龄相关的Rm缺陷可能反映了PFC和MTL区域之间的脱节。为了研究这一问题，我们将在功能(活动相关性)和解剖(扩散张量成像测量的白质完整性)方面将年龄相关的RM表现变化与PFC-MTL连接性的变化联系起来。综上所述，这些研究的结果将阐明与年龄相关的RM缺陷的神经关联，并将对促进健康具有重要意义。

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.