The essential circuit for both item and associative stimulus recognition in any given sensory modality consists of the relevant cortical sensory processing stream(s), the medial temporal periallocortex (i.e. posterior parahippocampal, perirhinal, and entorhinal cortices), the ventromedial prefrontal cortex, and the medial dorsal nucleus of the thalamus. Context-free recall, familiarity based recognition, or fact memory, seems to depend primarily on the above basic memory circuit. Associative recall, recollection-based recognition, or event memory, seems to depend in addition on a higher-order circuit superimposed on the basic one and consisting of the hippocampus, mammillary body, and anterior thalamic nuclei. Several years ago we discovered that hypoxic ischemic events sustained within the first year of life may result in a form of amnesia. This 'developmental amnesia'(DA) is characterized by markedly impaired episodic (or event) memory combined with relative preservation of both semantic (or fact) memory and familiarity-based recognition memory, and is associated with medial temporal pathology that seems to be restricted to the hippocampus. In experimental animals, performance on a variety of spatial memory tasks depends on the integrity of the hippocampus. We therefore examined the extent to which patients with DA are impaired in navigational spatial memory. We investigated spatial recall using a virtual environment in a group of patients with DA, a group of patients with 'moderate'hippocampal damage, and a normal control group. The virtual environment consisted of a circular arena, with distal cues being present throughout the experiment to provide orientation. During learning, a circular boundary, as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall for all stimulus objects was tested with only the circular boundary or the landmark being present. The 'moderate'and control groups showed no difference in performance during either the learning phase or the test phase of the experiment. By contrast, patients with DA were markedly impaired in both phases of this task, exhibiting slower learning and significant impairment in both boundary-based and landmark-based spatial recall. Across groups, performance on both types of spatial recall was highly correlated with the overall memory quotient (MQ), but not with Full Scale IQ, age, or gender. Analysis of the relationship between task performance and intracerebral volume measures across groups revealed that boundary-based and landmark-based spatial recall were both most strongly related to bilateral hippocampal volumes. Volumes of the thalamus, caudate nucleus, and nucleus accumbens covaried with hippocampal volumes, but none of these explained spatial memory performance beyond that accounted for by the hippocampal volumes. These most recent results suggest that spatial recall in a virtual environment is impaired in patients with DA for both boundary-based and landmark-based navigation, and that both types of recall deficit are best explained by a reduction in bilateral hippocampal volumes. While a large body of evidence in humans supports the idea that recognition memory can be supported by both recollection and familiarity, it is so far unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. We trained monkeys on a visual running-recognition task with trial unique stimuli but in addition to the standard training we manipulated the monkeys bias to respond to old or new stimuli by manipulating the relative amount of reward that was obtainable for correct old and new responses. The resulting receiver operating characteristics (ROCs) were curvilinear, suggesting that a threshold process alone is not able to account for the data. Furthermore, these curves were significantly U-shaped, suggesting that a signal detection process alone cannot account for the data thus it is likely that recognition memory in monkeys, as in humans, is supported by two processes. Mnemonic associations are most often formed between events that are separated in time. Using magnetoencephalography in humans, we found that theta amplitude predicted whether the association between two temporally separated events, but not whether individual events, would later be remembered. Theta correlated with associative encoding either shortly before or after the second event, depending on whether the onset of the second event was temporally predictable or not. Furthermore, theta before the onset of the second event not only predicted associative memory formation, but also whether information about the first event could be simultaneously decoded from the neuromagnetic data. The results demonstrate how events separated in time can be mnemonically linked by a theta-mediated, temporally flexible retrieval process. Recognition consists of the relevant cortical sensory processing stream and the medial temporal cortex. Visual recognition memory is dependent upon the interaction of the visual association cortex of area TE and the adjacent perirhinal cortex. We recorded neural activity across all six layers simultaneously in the perirhinal and area TE while a subject was performing a running recognition memory task. Successful memory formation was accompanied by enhanced multi-unit activity in the upper-middle layers and deep layers of perirhinal cortex, but not in area TE. Current source densities revealed that successful memory formation was associated with enhanced high-gamma amplitude in superficial and deep layers of perirhinal cortex, but not in area TE. The laminar profile of recognition memory processes and their interaction within the perirhinal cortex may provide clues to better understand the network mechanisms that underlie perirhinal-dependent memory functions.
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| Munoz, M; Chadwick, M; Perez-Hernandez, E et al. (2011) Novelty preference in patients with developmental amnesia. Hippocampus 21:1268-76 |
| Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I et al. (2011) A new neural framework for visuospatial processing. Nat Rev Neurosci 12:217-30 |
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