The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer disease. Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of Alzheimer disease. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object [Yeung, L. K., Olsen, R. K., Bild-Enkin, H. E. P., D'Angelo, M. C., Kacollja, A., McQuiggan, D. A., et al. Anterolateral entorhinal cortex volume predicted by altered intra-item configural processing. Journal of Neuroscience , 37 , 5527–5538, 2017]. In this study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eye-tracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context [Wilson, D. I., Langston, R. F., Schlesiger, M. I., Wagner, M., Watanabe, S., & Ainge, J. A. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus , 23 , 352–366, 2013], and object-trace memory, the memory for the former location of objects [Tsao, A., Moser, M. B., & Moser, E. I. Traces of experience in the lateral entorhinal cortex. Current Biology , 23 , 399–405, 2013]. In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

Recent studies indicate that medial-temporal lobe (MTL) damage, either from focal lesions or neurodegenerative disease (e.g., semantic dementia), impairs perception as well as long-term declarative memory. Notably, however, these two patient groups show different performance for meaningful versus unfamiliar stimuli. In amnesics with nonprogressive MTL lesions, the use of meaningful stimuli, compared with unfamiliar items, boosted discrimination performance. In semantic dementia, a condition characterized by progressive deterioration of conceptual knowledge in the context of anterolateral temporal lobe damage, performance for meaningful stimuli was equivalent to that for unfamiliar items. To further investigate these findings, we scanned healthy volunteers while they performed odd-one-out discriminations involving familiar (i.e., meaningful/famous) and unfamiliar (i.e., novel) objects and faces and a baseline task of size oddity. Outside the scanner, volunteers' recognition memory was assessed. We found above baseline activity in the perirhinal cortex and hippocampus for all object and face discriminations and above baseline activity in the temporal pole for all face discriminations. The comparison of meaningful, relative to novel, faces and objects, revealed increased activity in the perirhinal cortex and hippocampus. In the temporal pole, we also found activity related to meaningfulness for faces but not for objects. Importantly, these meaningfulness effects were evident even for discriminations that were not subsequently well remembered, suggesting that the difference between meaningful and novel stimuli reflects perceptual or conceptual processes rather than solely incidental encoding into long-term memory. The results provide further evidence that the MTL is recruited during complex perceptual discrimination and additionally suggest that these structures are recruited in semantic processing of objects and faces.