Working Memory Training, Neural Correlates, and Aging

描述（由申请人提供）：工作记忆（WM）是一种基本的认知能力，在正常衰老过程中稳步下降。然而，越来越多的证据表明，通过训练，即使在老年人（OA）中，WM也有很大的改善潜力。特别是当自适应方法不断调整任务难度以适应性能水平的变化时，WM训练任务的性能可以得到显著而可靠的提高。虽然年轻人（YA）通常比OA获得更高的表现，并且随着时间的推移显示出更好的WM收益，OA受益于WM训练，并且在训练后数月仍能保持训练收益。关键的是，这种可塑性和年龄影响的机制在很大程度上是未知的。因此，本研究提出的重要问题是需要确定工作记忆可塑性的神经标记以及它们如何因年龄而不同。本研究利用功能性磁共振成像（fMRI）从三个方面探讨了WM训练任务改善的神经基础，这些目标是在神经回路补偿相关利用假说（CRUNCH）和其他假设的可塑性机制框架内提出的。CRUNCH提出，大脑激活和记忆负荷之间的关系是一个倒u函数，与年龄无关，正如具体目标所描述的那样。为了补偿与年龄相关的衰退，OA功能相对于YA功能向左移动，因此OA在较低负载下达到资源限制。该模型预测，训练应该提高神经效率，从而将YA和OA的功能向右转移，并增加大脑可以响应的任务要求的范围。CRUNCH框架还预测了差异性（通过多体素模式分析，MVPA测量）和功能连通性应如何因训练而变化。MVPA可以为特定领域资源的可塑性提供新的证据，而连通性分析可以揭示与WM训练相关的网络电路的可塑性。我们提出了一个训练实验（20 OA和20 YA），分别对三个目标(1)单变量、(2)多变量和(3)CRUNCH的连通性预测进行初步评估。拟议的研究将测试这些措施对YA和OA中WM培训的敏感性，以证明我们的方法的可行性，并为未来R01的功率估算、设计和数据分析决策建立强大的经验基础。通过识别训练收益背后可塑性的神经相关因素，未来的研究可以确定这些标记是否可以预测训练收益的大小和维持，转移的程度和限制，以及YA和OA中潜在的其他认知结果。干预措施的发展，即使是对WM功能的适度改善，特别是在老年人中，也可以潜在地保持有效的功能水平，避免进一步的衰退。

DESCRIPTION (provided by applicant): Working memory (WM) is a fundamental cognitive ability that declines steadily over the course of normal aging. Mounting evidence suggests however, that with training there is potential for considerable improvement in WM even in older adults (OA). Performance on the WM training tasks can improve markedly and reliably especially when adaptive methods continually adjust task difficulty to changing performance level. While younger adults (YA) typically achieve higher performance than OA and show greater preservation of WM gains over time, OA benefit from WM training, and sustain training benefits even months after training. Critically, the mechanisms underlying such plasticity and the effects of age are largely unknown. Thus, the significant problem addressed by the proposed research is the need to identify the neural markers of working memory plasticity and how they differ due to age. The proposed research uses functional magnetic resonance imaging (fMRI) to investigate the neural bases of improvement on a WM training task in three aims, framed within the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH), and other hypothesized mechanisms of plasticity. CRUNCH proposes that the relationship between brain activation and memory load is an inverted-U function regardless of age, as depicted in the specific aims. To compensate for age-related declines, the OA function is shifted left relative to the YA function and consequently OA reach a resource limit at lower loads. This model predicts that training should increase neural efficiency thereby shifting the functions rightward, for both YA and OA, and increasing the range of task demands to which the brain can respond. The CRUNCH framework also makes predictions about how distinctiveness (as measured with multi-voxel pattern analyses, MVPA) and functional connectivity should change due to training. MVPA can provide new evidence about plasticity of domain-specific resources, and connectivity analyses can reveal the plasticity of network circuitry associated WM training. We propose one training experiment (with 20 OA and 20 YA) to conduct a preliminary assessment of (1) univariate, (2) multivariate, and (3) connectivity predictions of CRUNCH in three aims (respectively). The proposed research will test the sensitivity of these measures to WM training in YA and OA in order to demonstrate the feasibility of our approach and establish a strong empirical base to inform power estimates, design and data analysis decisions for a future R01. By identifying the neural correlates of the plasticity underlying training gains, future research cn determine whether such markers can predict the magnitude and maintenance of training gains, the extent and limits of transfer and potentially other cognitive outcomes in YA and OA. The development of interventions that achieve even modest improvements of WM function, especially in the elderly, can potentially maintain effective levels of functioning and stave off further decline.