Aging hippocampus and cognitive control in health and MCI

摘要/总结 认知控制包括主动（目标导向）和反应（刺激驱动）过程，对日常生活至关重要。 老年人的功能。然而，衰老如何影响主动和被动控制仍不清楚， AX-连续执行任务（AX-CPT）的研究报告了受损的主动控制但完整的反应控制 而停止信号任务（SST）的研究则报告了相反的情况。此外，大脑的结构和功能 认知控制的年龄依赖性变化的基础尚未得到系统的研究。我们的目标是雇用 一个创新的实验设计，以解决这一差距的研究。根据文献和我们的 初步研究结果，我们将调查海马功能障碍和损害的背景处理， 在老年和轻度认知障碍（MCI）个体中，这是认知控制缺陷的决定因素。 具体来说，我们的目标是研究如何上下文表示（即，显式刺激-反应映射 AX-CPT和SST中的隐式推理）而不是运动需求（即，AX-CPT中的无所不在的反应 以及SST中的条件反应）有助于认知控制中与年龄相关的缺陷。通过包括两 行为任务的变体AXn-CPT，其中非目标响应被替换为无响应，以及 SSTr，其中停止信号指示替代运动响应而不是无响应，我们建议 区分心理结构，决定年龄和MCI相关的变化，主动和被动 控制通过结合行为任务和功能磁共振成像，我们将研究结构和功能的大脑 这些变化解释了认知控制中与年龄和MCI相关的改变。首先，我们假设，如果上下文 表征解释了衰老和MCI的影响，衰老将与受损的主动性和 AX-CPT和AXn-CPT中反应性控制完好， SST和SSTR。相反，如果运动需求占影响，老年人将表现出受损 AX-CPT和SSTr中的主动和完整反应性控制，以及完整的主动和受损的反应性控制 SST和AXn-CPT中的对照。第二，我们假设控制缺陷与干扰有关， 海马和其他任务相关区域的激活和功能连接。特别是 前海马和后海马在支持反应性控制和主动性控制中可能发挥不同的作用。第三、 我们假设海马和前额叶皮质灰质体积与年龄相关的减少，并将探讨 这种结构性缺陷如何与认知控制过程中功能激活的年龄依赖性改变相关。 此外，海马体中不成比例的体积下降和改变的激活可能与 认知控制能力下降总之，拟议的研究将描绘心理和神经 衰老和MCI中执行控制功能障碍的潜在过程，解决了 衰老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信息。

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.