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.

Public Health Relevance

The proposed project investigates age-related changes in conceptual and perceptual memory-encoding processes mediated by the perirhinal cortex, a medial temporal lobe subregion. Perirhinal cortex damage is a strong predictor of many forms of dementia, particularly Alzheimer's disease and semantic dementia. Thus, the results of this project will not only directly inform the role of perirhinal cortex in memory-encoding processes, but will also direct translational work towards developing biomarkers for early diagnosis (e.g., perirhinal cortex dysfunction) and interventions targeting memory deficits (e.g., encoding strategies) found in both healthy and pathological aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Wagster, Molly V
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Duke University
Other Basic Sciences
Schools of Arts and Sciences
United States
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Wang, Wei-Chun; Wing, Erik A; Murphy, David L K et al. (2018) Excitatory TMS modulates memory representations. Cogn Neurosci 9:151-166
Wang, Wei-Chun; Brashier, Nadia M; Wing, Erik A et al. (2016) On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth. J Cogn Neurosci 28:739-46
Wang, Wei-Chun; Giovanello, Kelly S (2016) The Role of Medial Temporal Lobe Regions in Incidental and Intentional Retrieval of Item and Relational Information in Aging. Hippocampus 26:693-9