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. parahippocampal, rhinal cortices), the ventromedial prefrontal cortex, and the medial dorsal nucleus of the thalamus. Associative recall, on the other hand, appears to be organized hierarchically;whereas context-free recall, familiarity based recognition, or fact memory, seem to depend primarily on the above basic memory circuit, context-rich recall, recollection-based recognition, or event memory, seem 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 our studies of children conducted at the Developmental Cognitive Neuroscience Unit at the University College London Institute of Child Health discovered that hypoxic ischemic events sustained within the first year of life may result in a form of amnesia. We labeled this early-onset form, 'developmental amnesia'(DA), 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 pathology that seems to be restricted to the hippocampus. We have expanded our investigation to a larger population of children known to have been exposed to neonatal hypoxia/ischaemia. We examined three patient groups diagnosed as neonates with cardiorespiratory disease, cyanosis resulting from the Transposition of the Great Arteries, or extreme prematurity and compared them with healthy controls using voxel-based morphometry. None of the children had a history of known neurodevelopmental disorders or neurological impairments, and all attended mainstream schools. Compared with the controls, patients showed that reduced gray matter density in the hippocampus was significantly correlated with measures of delayed memory. The results support our initial proposal that neonatal hypoxia/ischaemia can result in chronic memory impairment due to bilateral hippocampal damage specifically. The dissociation in DA patients between impaired episodic and intact semantic memory appears to be accompanied by a second dissociation between a pronounced deficit in recall, along with preserved recognition. We compared a group of DA patients with healthy controls on tests of episodic memory, semantic memory, intelligence, literacy, numeracy, fluency, and recall and recognition. Scores for DA subjects were not different from controls on the non hippocampal-dependent measures of semantic memory, intelligence, literacy, numeracy and fluency. However, on hippocampal-dependent measures of episodic memory, DA group means were significantly lower than those of controls. Similarly, while recognition was preserved in the DA group, recall was severely impaired. Hence, the DA patient group showed intact semantic memory but impaired episodic memory, and intact recognition along with deficient recall as a result of marked hippocampal pathology. Dual-process models of recognition memory converge on the idea that both recollection and familiarity contribute to this mnemonic function. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was first encountered, whereas familiarity-based recognition lacks this context. There is a growing body of evidence in humans that supports the notion that recollection judgments are probabilistic in nature and items are only recognized if a threshold is exceeded, whereas familiarity judgments are based on a signal detection process, in that memory strength reflects a continuous scale with new and old items forming overlapping gaussian distributions. We tested DA patients on incidental recognition memory using a visual paired comparison task (VPC) to re-examine whether or not selective hippocampal damage reduces novelty preference. Compared with normal control subjects, the DA group showed a delay-dependent reduction in novelty preference on VPC. These results suggest that the hippocampus may contribute to some forms of recognition memory. However, this defect in recognition is difficult to reconcile with current views of purported hippocampal contribution to recognition which as mentioned above appear limited to task conditions that encourage recollection of an item. By contrast, VPC, throughout which the participant remains entirely uninstructed other than to view the stimuli, would likely lead to recognition based on familiarity rather than recollection or, alternatively, weak memories rather than strong. Two possibilities may resolve this apparent conflict and need to be investigated. One is that some variable in VPC, such as the extended period of stimulus encoding during familiarization, overrides its incidental nature, and, therefore promotes either recollection- or strength-based recognition, rendering the task hippocampal-dependent. The other possibility is that VPC, rather than providing a measure of incidental recognition, actually assesses an implicit, information-gathering process modulated by habituation, for which the hippocampus is also partly responsible, independent of its role in recognition. While a large body of evidence in humans supports the idea that recognition memory can be supported by both recollection and familiarity, it has so far been unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Recently we completed a behavioral study using receiver operating characteristics (ROCs). ROCs in recognition memory relate the proportion of correctly recognized repeated, or old, items to the proportion of incorrectly recognized novel distracters as a function of response bias. We trained monkeys on a visual running-recognition task with trial unique stimuli. We manipulated the monkeys bias to respond old or new by manipulating the relative amount of reward (juice) that was obtainable for correct old and new responses. ROCs were curvilinear, suggesting that a threshold process alone is not able to account for the data. Furthermore, the zROCs were significantly U-shaped, suggesting that a signal detection process alone cannot account for the data. Instead, a combination of a signal detection process and a threshold process can reliably characterize the empirical data. Thus, our results suggest that recognition memory in monkeys, as in humans, is supported by two processes. Evidence in monkeys indicates that the ventromedial frontal (VMF) cortex plays an important role in learning through its participation in a rhinal-VMF circuit. An earlier study demonstrated that even though rhinal (Rh) lesions produced greater deficits than VMF lesions in one-trial object recognition (DNMS) at delays of several minutes, the reverse was the case for relearning the DNMS rule at short (10-s) delays. In a follow-up study we asked whether relearning another type of rule, win-stay/lose shift (WSLS) with trial-unique objects, a rule that enables one-trial object-reward association, would likewise be impaired more severely by VMF than by Rh lesions. Animals with VMF lesions showed greater difficulty than those with Rh lesions in relearning the WSLS rule, a differential effect even larger than that obtained in the earlier study on recognition memory. The combined results support the view that VMF cortex mediates the attachment of reward value not only to objects but also to abstract or conceptual object classes (i.e. novel objects in the case of DNMS, and positive objects in the case of WSLS), thereby serving a critical function for both one-trial object recognition memory and one-trial object-reward associative memory.

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Geva, Sharon; Cooper, Janine M; Gadian, David G et al. (2016) Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy. Dev Cogn Neurosci 20:12-22
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