We investigated whether older adults without subjective memory complaints, but who present with cognitive decline in the laboratory, demonstrate atrophy in medial temporal lobe (MTL) subregions associated with Alzheimer's disease. Forty community-dwelling older adults were categorized based on Montreal Cognitive Assessment (MoCA) performance. Total gray/white matter, cerebrospinal fluid, and white matter hyperintensity load were quantified from whole-brain T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging scans, whereas hippocampal subfields and MTL cortical subregion volumes (CA1, dentate gyrus/CA2/3, subiculum, anterolateral and posteromedial entorhinal, perirhinal, and parahippocampal cortices) were quantified using high-resolution T2-weighted scans. Cognitive status was evaluated using standard neuropsychological assessments. No significant differences were found in the whole-brain measures. However, MTL volumetry revealed that anterolateral entorhinal cortex (alERC) volume-the same region in which Alzheimer's pathology originates-was strongly associated with MoCA performance. This is the first study to demonstrate that alERC volume is related to cognitive decline in undiagnosed community-dwelling older adults.

Recent research on cognitive control has focused on the learning consequences of high selective attention demands in selective attention tasks (e.g., Botvinick, 2007;. The current study extends these ideas by examining the influence of selective attention demands on remembering. In Experiment 1, participants read aloud the red word in a pair of red and green spatially interleaved words. Half of the items were congruent (the interleaved words had the same identity), and the other half were incongruent (the interleaved words had different identities). Following the naming phase, participants completed a surprise recognition memory test. In this test phase, recognition memory was better for incongruent than for congruent items. In Experiment 2, context was only partially reinstated at test, and again recognition memory was better for incongruent than for congruent items. In Experiment 3, all of the items contained two different words, but in one condition the words were presented close together and interleaved, while in the other condition the two words were spatially separated.Recognition memory was better for the interleaved than for the separated items. This result rules out an interpretation of the congruency effects on recognition in Experiments 1 and 2 that hinges on stronger relational encoding for items that have two different words. Together, the results support the view that selective attention demands for incongruent items lead to encoding that improves recognition.3

Recent functional imaging studies have proposed that the human entorhinal cortex (ERC) is subdivided into functionally distinct anterolateral (alERC) and posteromedial (pmERC) subregions. The alERC overlaps with regions that are affected earliest by Alzheimer's disease pathology, yet its cognitive function remains poorly understood. Previous human fMRI studies have focused on its role in object memory, but rodent studies on the putatively homologous lateral entorhinal cortex suggest that it also plays an important role in representing spatial properties of objects. To investigate the cognitive effects of human alERC volume differences, we developed an eye-tracking-based task to evaluate intra-item configural processing (i.e., processing the arrangement of an object's features) and used manual segmentation based on a recently developed protocol to delineate the alERC/pmERC and other medial temporal lobe (MTL) subregions. In a group of older adult men and women at varying stages of brain atrophy and cognitive decline, we found that intra-item configural processing, regardless of an object's novelty, was strongly predicted by alERC volume, but not by the volume of any other MTL subregion. These results provide the first evidence that the human alERC plays a role in supporting a distinct aspect of object processing, namely attending to the arrangement of an object's component features.

Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255‐257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A‐>B, B‐>C, C‐>D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A‐>C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre‐experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre‐experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to‐be‐learned relations were arbitrary. However, accuracy improved for older adults when they could use pre‐experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and anterior temporal regions may have resulted in an inability to use prior knowledge to flexibly express indirect relational knowledge. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Recently, the amnesic case D.A. was shown to circumvent his relational memory impairments, as observed in the transverse patterning (TP) task, using a self-generated unitization strategy, and such performance benefits were maintained over extended delays (Ryan et al., 2013). "Unitization" encourages fusing of distinct items, through an action, into a single unit from which the relations among the items may then be derived. Here, we provide the first documentation of the developmental amnesic case, N.C., who presents with relatively circumscribed lesions to the extended hippocampal system, and with impaired episodic memory. Despite impairments on standard versions of TP, N.C. benefited from unitization, showed evidence of transfer to novel stimuli, and maintained his performance over extended delays. These findings suggest that self-generation is not a requirement for the successful implementation of unitization, and further provides the first evidence of rapid transfer and long-lasting success of a learning strategy in a human amnesic case.

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.

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer's disease (AD). Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of AD. 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 . In the present 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 eyetracking 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 et al., 2013), and object-trace memory, the memory for the former location of objects (Tsao, Moser, & Moser, 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 (PHC) selectively predicted object-in-place memory, but not objecttrace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

The present study examines the effect of immediate repetition on recognition memory. In a series of 4 experiments, the study phase task was to name aloud a word that was immediately preceded by either the same word (repeated trials) or a different word (not-repeated trials). Across experiments, performance in the study phase demonstrated the anticipated benefit in naming times for repeated trials. More important, performance in the test phase revealed greater sensitivity for not-repeated than repeated trials. This effect was observed even when repetitions at study were separated by an unrelated word (Experiment 3), and was eliminated only when participants named both words in succession at study (Experiment 4). These findings fit nicely with the desirable difficulty principle (R. A. Bjork, 1994), as they demonstrate that items more easily processed at study (i.e., repeated items) are not as well-encoded as items that are more difficult to process at study (i.e., not-repeated items). Furthermore, the current study points to the possibility that attentional orienting in response to processing difficulty may constitute a broadly important cognitive control adaptation that impacts memory encoding.