Aging and components of cognitive control in associative memory

 描述(由申请人提供)：健康的衰老，即使在没有痴呆症的情况下，也与记忆力下降有关，特别是与以前遇到的事件相关的细节。这种联想记忆的年龄相关损害是普遍存在的，前额叶皮质(PFC)介导的认知控制功能障碍，如比较推理，是导致这些损害的主要因素。现有的认知老化理论提出了单一的、非特异性的PFC改变。我们认为，这些理论过分简化了PFC在年龄相关记忆障碍中的作用。我们提出了一个新的“衰老中的联想记忆控制”模型，该模型具有清晰的可检验预测，将提供受衰老影响的精确控制功能和相关神经网络的知识。我们的模型预测，在联想记忆编码和提取过程中，年龄对“高阶”控制操作的影响大于“低阶”控制操作。我们对区域特定和分布的活动模式以及控制功能的时间进程做出了具体预测。因此，我们将采用一种新的多管齐下的方法，利用互补的行为、单变量和多变量功能磁共振成像(FMRI)技术和事件相关电位(ERP)来解决以下特定目标：(1)我们预测支持编码过程中多个关系整合的头端PFC“高阶”过程的功能障碍有助于年龄相关的联想记忆障碍。我们预测在左侧尾侧PFC支持的“一阶”项目选择和“二阶”项目间关系编码过程中，存在最小的功能障碍。我们预测，多变量fMRI分析将显示，包含吻侧PFC的编码网络中功能连接性的降低导致联想记忆性能较差。(2)我们预测，在提取过程中支持多个被提取的联想整合的PFC“高阶”加工的功能障碍会导致与年龄相关的联想记忆障碍。我们预测在右侧尾侧PFC支持的检索后监测过程中，存在轻微的功能障碍。我们预测，多变量fMRI分析将显示，包含吻侧PFC的检索网络中功能连接的减少导致了较差的联想记忆性能。我们预测，在记忆恢复后，索引这些控制功能的事件相关电位将被激活。检索后的事件相关电位标记头PFC，而不是尾部PFC的功能会随着年龄的增长而减弱。将区域激活的单变量测量与功能连通性和事件相关电位的多变量测量相结合，将提供对衰老如何影响PFC功能和记忆的更完整的理解。这些结果对于开发干预措施，通过针对衰老中的特定认知控制功能来改善联想记忆功能将是至关重要的。

 DESCRIPTION (provided by applicant): Healthy aging, even in the absence of dementia, is associated with memory decline, particularly for details associated with previously encountered events. Age-related impairments in this associative type of memory are pervasive and dysfunction in prefrontal cortical (PFC) mediated cognitive control functions like comparative reasoning is a major contributor to these impairments. Existing theories of cognitive aging propose unitary, non-specific PFC changes. We contend that such theories oversimplify the role of the PFC in age-related memory impairments. We propose a new "control of associative memory in aging" model with clear testable predictions that will provide knowledge of the precise control functions and related neural networks affected by aging. Our model predicts that the effects of age are greater for "high order" than "lower order" control operations during associative memory encoding and retrieval. We make concrete predictions about both regionally specific and distributed patterns of activity as well as the time course of control functions. Consequently, we will employ a novel multipronged approach utilizing complementary behavioral, univariate and multivariate functional magnetic resonance imaging (fMRI) techniques, and event-related potential (ERP) to address the following specific aims: (1) We predict that dysfunction in rostral PFC "high order" processes that support integration of multiple relationships during encoding contributes to age-related associative memory impairments. We predict minimal dysfunction in left caudal PFC supported "1st order" item selection and "2nd order" inter-item relational encoding processes. We predict that multivariate fMRI analyses will show that reduced functional connectivity within an encoding network containing the rostral PFC contributes t0 poor associative memory performance. (2) We predict that dysfunction in rostral PFC "high order" processes that support integration of multiple retrieved associations during retrieval contributes to age-related associative memory impairments. We predict minimal dysfunction in right caudal PFC supported post-retrieval monitoring processes. We predict that multivariate fMRI analyses will show that reduced functional connectivity within a retrieval network containing the rostral PFC contributes t0 poor associative memory performance. We predict that ERPs indexing these control functions will be engaged after memory recovery. Post-retrieval ERPs indexing rostral PFC but not caudal PFC functions will be attenuated by aging. The combination of univariate measures of regional activation alongside multivariate measures of functional connectivity and ERPs will provide a more complete understanding of precisely how aging affects PFC function and memory. These results will be essential in developing interventions to improve associative memory functioning by targeting specific cognitive control functions in aging.