Aging Changes to Perceptual and Conceptual Encoding in Perirhinal Cortex

描述（由申请人提供）：周围皮层（PRC）是内侧颞叶亚区（MTL），对于陈述性记忆过程（如基于熟悉度的识别）是必要的。相反，海马体（HC）对基于回忆的识别至关重要。大量研究健康老年人MTL亚区结构和功能完整性的工作表明，PRC和熟悉度相对于HC和回忆而言是次要的。相反，与年龄相关的神经认知障碍，如阿尔茨海默病，与广泛的MTL病理和记忆障碍有关。这种分离可以作为病理性衰老和痴呆症早期诊断的潜在生物标志物。然而，最近的研究对这种分离提出了挑战，因为有证据表明，与年龄相关的PRC在知觉区分中功能障碍，以及与年龄相关的PRC体积下降与熟悉性障碍有关。这些数据提高了在某些条件下老年人PRC功能受损的可能性。考虑到痴呆的早期诊断和认知训练和康复的含义，理解这种情况的界限是至关重要的。根据其解剖结构和连通性，PRC被建议分为侧面和内侧部分，分别支持感知和概念处理。与此一致的是，来自两方面工作的证据表明，PRC既支持知觉表征，也支持概念表征，这些表征有助于随后的熟悉性，尽管这些不同的文献没有进行系统的比较。鉴于老年人的知觉与概念加工受损的证据，在健康的老年人中，知觉编码受损可能是PRC功能障碍和记忆障碍的原因。两项拟议的fMRI研究探讨了侧PRC和内侧PRC是否分别支持知觉和概念加工，以及在健康衰老中是否前者而后者不受影响。研究1考察了与随后熟悉程度相关的概念（如单词）和知觉（如面孔）辨别的年龄相关变化，以及这些过程在多大程度上受到外侧和内侧PRC的支持。研究2探讨了与年龄相关的差异功能和结构连接网络的变化，这些网络与外侧和内侧PRC支持随后对编码对象（包括概念和感知细节）的概念和感知熟悉。为了评估外侧和内侧PRC对感知和概念信息的敏感性，我们建议检查单变量活动、多体素模式分析（MVPA）和功能连接预测随后熟悉程度的程度。此外，我们将评估行为与外侧和内侧PRC功能和体积之间关系的个体差异，以及白质（弥散张量成像）与支持感知和概念过程的其他皮质区域的完整性。这些分析使我们能够更好地理解健康老龄化如何以及在多大程度上影响被认为在中国服务于熟悉度的概念和感知表征。

DESCRIPTION (provided by applicant): The perirhinal cortex (PRC), a medial temporal lobe subregion (MTL), is necessary for declarative memory processes such as familiarity-based recognition. In contrast, the hippocampus (HC) is critical for recollection- based recognition. Considerable work investigating the structural and functional integrity of these MTL subregions in healthy aging indicates that PRC and familiarity are spared relative to HC and recollection. In contrast, age-related neurocognitive disorders such as Alzheimer's disease are associated with broad MTL pathology and memory impairments. This dissociation serves as a potential biomarker of pathological aging and early diagnosis of dementias. However, recent work challenges this dissociation, as there is evidence of age-related PRC dysfunction in perceptual discriminations and evidence that age-related decrements in PRC volume are related to familiarity impairments. These data raise the possibility of impaired PRC function in older adults under certain conditions. It is critical to understand the boundaries of such conditions given the implications for both early diagnosis of dementias and cognitive training and rehabilitation. Based on its anatomy and connectivity, PRC has been proposed to be divisible into lateral and medial portions that respectively support perceptual and conceptual processing. Consistent with this, there is evidence from two lines of work that PRC supports both perceptual and conceptual representations that can subserve subsequent familiarity, although these disparate literatures have not systematically compared. Given evidence of impaired perceptual relative to conceptual processing in older adults, it may be the case that impaired perceptual encoding accounts for PRC dysfunction and memory impairments in healthy aging. The two proposed fMRI studies explore whether lateral and medial PRC respectively supports perceptual and conceptual processing, and whether the former but not the latter is affected in healthy aging. Study 1 examines age-related changes in conceptual (e.g., word) and perceptual (e.g., face) discriminations that relate to subsequent familiarity, and the extent to which these processes are supported by lateral and medial PRC. Study 2 explores age-related changes in differential functional and structural connectivity networks with lateral and medial PRC supporting the subsequent conceptual and perceptual familiarity of encoded objects (which contain both conceptual and perceptual details). To assess the sensitivity of lateral and medial PRC to perceptual and conceptual information, we propose to examine the extent to which univariate activity, multi- voxel pattern analysis (MVPA), and functional connectivity predicts subsequent familiarity. Moreover, we will assess individual differences in the relationship between behavior and lateral and medial PRC function and volume, as well as white matter (diffusion tensor imaging) integrity with other cortical regions supporting perceptual and conceptual processes. These analyses allow us to better understand how and to what extent healthy aging affects conceptual and perceptual representations thought to subserve familiarity in PRC.