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Humans have the capacity to form new memories of events that are, at times, highly similar to events experienced in the past, as well as the capacity to integrate and associate new information within existing knowledge structures. The former process relies on mnemonic discrimination and is believed to depend on hippocampal pattern separation, whereas the latter is believed to depend on generalization signals and conceptual categorization supported by the neocortex. Here, we examine whether and how the ventromedial prefrontal cortex (vMPFC) supports discrimination and generalization on a widely used task that was primarily designed to tax hippocampal processes. Ten individuals with lesions to the vMPFC and 46 neurotypical control participants were administered an adapted version of the mnemonic similarity task [Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia, 51, 2442-2449, 2013], which assesses the ability to distinguish previously learned images of everyday objects (targets) from unstudied, highly similar images (lures) and dissimilar images (foils). Relative to controls, vMPFC-lesioned individuals showed intact discrimination of lures from targets but a propensity to mistake studied targets and similar lures for dissimilar foils. This pattern was accompanied by inflated confidence despite low accuracy when responding to similar lures. These findings demonstrate a more general role of the vMPFC in memory retrieval, rather than a specific role in supporting pattern separation., (© 2023 Massachusetts Institute of Technology.)

Pattern separation, the creation of distinct representations of similar inputs, and statistical learning, the rapid extraction of regularities across multiple inputs, have both been linked to hippocampal processing. It has been proposed that there may be functional differentiation within the hippocampus, such that the trisynaptic pathway (entorhinal cortex > dentate gyrus > CA3 > CA1) supports pattern separation, whereas the monosynaptic pathway (entorhinal cortex > CA1) supports statistical learning. To test this hypothesis, we investigated the behavioral expression of these two processes in B. L., an individual with highly selective bilateral lesions in the dentate gyrus that presumably disrupt the trisynaptic pathway. We tested pattern separation with two novel auditory versions of the continuous mnemonic similarity task, requiring the discrimination of similar environmental sounds and trisyllabic words. For statistical learning, participants were exposed to a continuous speech stream made up of repeating trisyllabic words. They were then tested implicitly through a RT-based task and explicitly through a rating task and a forced-choice recognition task. B. L. showed significant deficits in pattern separation on the mnemonic similarity tasks and on the explicit rating measure of statistical learning. In contrast, B. L. showed intact statistical learning on the implicit measure and the familiarity-based forced-choice recognition measure. Together, these results suggest that dentate gyrus integrity is critical for high-precision discrimination of similar inputs, but not the implicit expression of statistical regularities in behavior. Our findings offer unique new support for the view that pattern separation and statistical learning rely on distinct neural mechanisms., (© 2023 Massachusetts Institute of Technology.)

There is an inconsistency regarding the relationship between thinking about personal past experiences during autobiographical memory (AM) and thinking about other people's mental states during theory of mind (ToM). Neuroimaging studies of AM and ToM consistently report overlap in the brain regions recruited. Lesion data, however, show that amnesic people with AM impairment can have intact ToM, suggesting that distinct neural mechanisms support these abilities [Rosenbaum, R. S., Stuss, D. T., Levine, B., & Tulving, E. Theory of mind is independent of episodic memory. Science, 318, 1257, 2007]. The current fMRI study examined the functional and neural correlates of remembering one's own experiences in response to personal photos (AM condition) and imagining others' experiences in response to strangers' photos (ToM condition). AM and ToM conditions were matched in terms of content and vividness, and were compared directly and to a common baseline. Analyses revealed common activity within frontal and temporal-parietal regions, yet midline structures exhibited greater activity during AM. More specific analyses of event construction and detail elaboration revealed unique activation of the right hippocampus during AM construction, and of lateral regions, such as the right temporo-parietal junction (TPJ) during ToM elaboration. Moreover, a region of left hippocampus/perirhinal cortex appeared to be driven by event vividness. Thus, differences in AM and ToM emerge when a common baseline is used and temporal dynamics are taken into account. Furthermore, the right TPJ and related lateral regions, and not the hippocampus, may be needed for ToM, given that this ability is intact in amnesic people.

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of one's personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.

Recent research suggests that the hippocampus is not needed for the maintenance and recovery of extensively used environments learned long ago. Instead, a network of neocortical regions differentially supports memory for locationnavigation knowledge and visual appearance of well-known places. In this study, we present a patient, S. B., who was diagnosed with probable Alzheimer's disease long after retiring from his 40 years as a taxi driver in downtown Toronto, a place that he has visited rarely, if ever, in the last decade. His performance was compared to that of two other retired taxi drivers, L. R., who developed encephalitis after retirement, and I. L., who is without neurological illness, and a group of eight healthy control participants who were never taxi drivers but all of whom worked or lived in downtown Toronto until at least 10 years ago. Despite S. B.'s widespread atrophy, which has affected mainly his hippocampus and part of his occipitotemporal cortex, he performed at least as well as all other participants on remote memory tests of spatial location and mental navigation between well-known Toronto landmarks. Unlike the comparison populations, however, he was unable to discriminate between the appearances of landmarks that he had visited frequently in his many years as a taxi driver from unknown buildings. This profound deficit extended to famous world landmarks but not to famous faces and does not appear to be semantic in nature. These findings add further support to the claim that the hippocampus is not necessary for mental navigation of old environments and suggest that expertise is not sufficient to protect against landmark agnosia.