Aging hippocampus and cognitive control in health and MCI

摘要/摘要 认知控制包括主动(目标导向)和反应性(刺激驱动)过程，认知控制对日常生活至关重要 为老年人提供的功能。然而，衰老如何影响主动性和反应性控制仍不清楚， AX-持续执行任务(AX-CPT)报告的主动但完整的反应控制受损的研究 而对停车信号任务(SST)的研究则报告了相反的情况。此外，大脑的结构和功能 认知控制随年龄变化的基础还没有得到系统的研究。我们的目标是 一种创新的实验设计，以弥补研究中的这一差距。在文献的基础上和我们的 初步发现，我们将研究海马区功能障碍和上下文加工中的损伤 老年人和轻度认知障碍(MCI)患者认知控制缺陷的决定因素。 具体地说，我们的目标是研究语境表征(即，在 AX-CPT和SST中的隐含推理)而不是电机需求(即，AX-CPT中的无处不在的响应 以及SST中的条件反应)导致与年龄相关的认知控制缺陷。通过包括两个 行为任务的变体，AXN-CPT，其中非目标响应被无响应取代，以及 SSTR，在停止信号指示替代电机响应而不是无响应的情况下，我们建议 区分与年龄和MCI相关的主动性和反应性变化的心理结构 控制力。通过结合行为任务和功能磁共振成像，我们将研究大脑的结构和功能 这些变化可以解释与年龄和MCI相关的认知控制变化。首先，我们假设，如果与上下文相关， 表征解释了老龄化和MCI的影响，老龄化将与主动性和主动性受损相关 AX-CPT和AXN-CPT的完整无功控制，并具有完整的主动无功控制和受损无功控制 SST和SSTR。相反，如果汽车需求是造成这种影响的原因，老年人就会表现出受损 AX-CPT和SSTR中的主动和完整的反应控制，以及完整的主动和受损的反应 在SST和AXN-CPT中的控制。其次，我们假设控制不力与混乱有关 海马区和其他任务相关区域的激活和功能连接。尤其是， 前部和后部海马区可能在支持反应性和主动性控制方面发挥不同的作用。第三, 我们假设与年龄相关的海马区和前额叶皮质灰质体积减少，并将探索 在认知控制过程中，这种结构性缺陷如何与年龄相关的功能激活变化有关。 此外，海马区不成比例的体积下降和激活改变可能与 MCI患者认知控制能力下降。总之，这项拟议的研究将描绘出心理和神经 老龄化和MCI中潜在的执行控制功能障碍的过程，解决在以下方面的研究的关键差距 老化的神经科学。我们希望这些发现能为老年人的健康和疾病护理提供参考。

ABSTRACT/SUMMARY Comprising proactive (goal-directed) and reactive (stimulus-driven) processes, cognitive control is critical to daily functions for older adults. However, how aging influences proactive and reactive control remains unclear, with studies of the AX-continuous performance task (AX-CPT) reporting impaired proactive but intact reactive control and studies of the stop signal task (SST) reporting the opposite. Further, the structural and functional cerebral bases of age-dependent changes in cognitive control have not been studied systematically. We aim to employ an innovative experimental design to address this gap in research. On the basis of the literature and our preliminary findings, we will investigate hippocampal dysfunction and impairment in contextual processing as a determinant of cognitive control deficits during aging and in individuals with mild cognitive impairment (MCI). Specifically, we aim to examine how contextual representation (i.e., explicit stimulus-response mapping in the AX-CPT and implicit inference in the SST) rather than motor demand (i.e., omnipresent response in the AX-CPT and conditional response in the SST) contribute to age-related deficits in cognitive control. By including two variants of the behavioral tasks, the AXn-CPT, where non-target response is replaced with no response, and SSTr, where stop signal instructs an alternative motor response instead of no response, we propose to distinguish the psychological constructs that dictate age- and MCI-related changes in proactive and reactive control. By combining the behavioral tasks and fMRI we will investigate how structural and functional brain changes account for age- and MCI-related alterations in cognitive control. First, we hypothesize that, if contextual representation accounts for the effects of aging and MCI, aging will be associated with impaired proactive and intact reactive control in both AX-CPT and AXn-CPT, and with intact proactive and impaired reactive control in both SST and SSTr. Conversely, if motor demand accounts for the effects, older adults will show impaired proactive and intact reactive control in AX-CPT and SSTr, as well as intact proactive and impaired reactive control in SST and AXn-CPT. Second, we hypothesize that deficient control is associated with disrupted activation and functional connectivity in the hippocampus and other task-related regions. In particular, the anterior and posterior hippocampus may play distinct roles in supporting reactive and proactive control. Third, we hypothesize age-related decreases in hippocampal and prefrontal cortical gray matter volume and will explore how this structural deficit relates to age-dependent alterations in functional activations during cognitive control. Further, disproportionate volumetric decline and altered activations in the hippocampus may be associated with deteriorated cognitive control in MCI. Together, the proposed study will delineate the psychological and neural processes underlying executive control dysfunction in aging and MCI, addressing a critical gap of research in aging neuroscience. We hope that the findings would inform the care of older adults in health and illness.