Deficits in top-down processes during episodic memory in aging and preclinical AD

描述(申请人提供)：尽管情节记忆传统上与内侧颞叶系统有关，但很明显，由额顶区辅助的自上而下的过程与该系统相互作用，以影响什么信息被编码。自上而下的流程(即控制流程)起源于“顶部”区域(即额顶)，并影响“底部”感觉运动区，以完成目标导向行为。鉴于成功的编码取决于将注意力引导到相关信息以及抑制无关信息，因此随后的记忆对比(随后记住的项目与忘记的项目的激活)揭示了FP的激活也就不足为奇了。尽管情景记忆编码过程中自上而下加工的相关性可以通过检测与后续记忆效应相关的激活来推断，但很少有研究实现在记忆编码过程中改变自上而下加工的设计。此外，内侧颞叶和FP网络的功能障碍在衰老过程中一直被报道，目前还不清楚这些网络的破坏如何影响衰老时的记忆表现。有趣的是，相当一部分临床正常的老年人的β-淀粉样蛋白(A？)水平升高。斑块，一种与阿尔茨海默病(AD)密切相关的病理。研究了早期A的相关性？沉积表明，这种病理可能是一种启动事件，导致神经元功能障碍和神经退行性变，认知丧失，最终导致AD。在这一框架内，临床正常的高水平A？被认为是阿尔茨海默病(“临床前阿尔茨海默病”)的最早迹象，从最初的病理堆积到临床痴呆症的发作大约延迟10年。因此，了解这一临床前阶段对于在阿尔茨海默病中典型的广泛损害发生之前揭示A？诱导的神经元功能障碍的潜在机制是至关重要的。尽管对临床前阿尔茨海默病的研究集中在情景记忆下降(因为这个领域是第一个显示AD下降的领域)，但有可能 这种病理对额顶区调节的自上而下的过程有影响。例如，A？沉积在整个额顶区非常普遍，执行功能的下降已知发生在接近AD诊断的地方。因此，本提案的总体目标是纳入自上而下过程的组成部分(即。选择性注意和任务切换)在情节记忆设计中，以更好地理解年龄和A？额顶区的激活模式。

DESCRIPTION (provided by applicant): Although episodic memory is traditionally associated with the medial temporal lobe system, it is clear that top-down processes subserved by frontoparietal regions interact with this system to influence what information is encoded. Top-down processes (ie. control processes) originate in "top" regions (ie. frontoparietal) and influence "bottom" sensorimotor regions to complete goal directed behavior. Given that successful encoding depends on directing attention to towards relevant information as well as inhibiting irrelevant information, it is not surprising that subsequent memory contrasts (activatio for subsequently remembered versus forgotten items) reveals FP activation. Although the relevance of top-down processes during episodic memory encoding can be inferred by examining activation related to subsequent memory effects, few studies have implemented a design that varies top-down processes during memory encoding. Furthermore, dysfunction in medial temporal lobe and FP networks is consistently reported in aging, and it is unclear how disruption within these networks influences memory performance in aging. Interestingly, a substantial proportion number of clinically normal elderly individuals have elevated levels of beta-amyloid (A?) plaques, a pathology strongly associated with Alzheimer's disease (AD). Research investigating the relevance of early A? deposition suggests this pathology may be an initiating event that leads to neuronal dysfunction and neurodegeneration, cognitive loss and eventually AD. Within this framework, clinically normal individuals with high levels of A? are thought to represent the earliest signs of Alzheimer's disease ("preclinical AD"), with a delay of approximately 10 years between initial pathological accumulation and the onset of clinical dementia. Thus, an understanding of this preclinical stage is of utmost importance to uncover mechanisms underlying A?-induced neuronal dysfunction before the widespread damage that is typical in AD has occurred. Although research examining preclinical AD has focused on episodic memory decline (since this domain is the first to show decline in AD), it is possible that this pathology has an impact on top-down processes mediated by frontoparietal regions. For instance, A? deposition is highly prevalent throughout frontoparietal regions and decline in executive function is known to occur in close proximity to AD diagnosis. Thus, the overall goal of this proposal is to incorporate components of top-down processes (ie. selective attention and task switching) in an episodic memory design to better understand effects of age and A? on patterns of activation in frontoparietal regions.