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 magnocellular division of the medial dorsal nucleus of the thalamus. Associative recall, on the other hand, appears now to be organized hierarchically;thus, whereas context-free recall, or fact memory, seems to depend primarily on the above basic memory circuit, context-rich recall, 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. That item recognition at least does not depend on the higher-order memory circuit is supported by evidence obtained in our earlier studies of children conducted at the Developmental Cognitive Neuroscience Unit (DCNU) in the UCL/ICH. In our early experiments we discovered that hypoxic ischemic events sustained within the first year of life may result in a form of amnesia that appears to differ from the global anterograde amnesia commonly reported in adult-onset cases. 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 medial temporal pathology that seems to be restricted to the hippocampus. Whether their relatively spared recognition ability is due to restriction of their medial temporal lobe damage to the hippocampus or whether it is due to their early age at injury is not certain. Incidental recognition memory is the spontaneous ability to discriminate novel objects from familiar ones. This type of recognition is reflected in the automatic attraction of ones gaze by novel objects, i.e. novelty preference, a behavior consistently observed across species, including monkeys and humans. DA patients and normal controls were examined using a visual paired comparison task. Preferential looking to a new stimulus, measured by monitoring eye fixation, signals recognition of a previously presented stimulus as familiar. DA patients preferential looking to novel stimuli equaled that of controls at 0 and 5 s delays between initial and second stimulus presentations, however it was impaired relative to controls at delays of 30 to 120s. Indeed DA patients performance fell to near chance levels. These results indicate that the integrity of the hippocampus is required for delayed incidental recognition in humans. Furthermore it suggests that neural plasticity during development does not allow other structures or circuits to substitute for the damaged hippocampus. We have now examined two new cohorts of children, those who as neonates were treated with extra corporeal membrane oxygenation to treat cardiorespiratory disease or who underwent corrective surgery to repair a common form of congential heart disease. To determine the incidence of selective memory problems we compared 45 children treated for cardiorespiratory distress with 57 age matched controls on standardized tests of everyday memory, general memory, immediate and delayed recall, and IQ. The patient group had scores within the normal range on the non-hippocampal dependent tests of intelligence, literacy, factual and working memory. In contrast on the measures of everyday memory and general memory they showed below average ability. Volumetric analysis of the hippocampus using MRI showed the patients who scored >1.5 SDs below the standard mean on the general memory quotient yet with normal IQ, had a mean reduction of 17% in hippocampal volume relative to controls. Thus a significant proportion of neonates who have suffered hypoxia/ischemia in association with cadiorespiratory disease treatment go on to develop memory deficits later in life. That associative recognition in monkeys also does not depend on the higher-order memory circuit (but does require the basic circuit) is supported by our evidence on spatial memory. In an early study of one-trial memory for object-place association, a severe and chronic impairment was observed after ablation of the hippocampal formation (HF) and subjacent cortex. In follow-up studies, we found that this memory impairment is critically dependent not on the HF but rather on the subjacent posterior parahippocampal (PH) region. Ibotenic acid lesions (ibo) restricted to the HF, sparing the underlying PH cortex and fibers of passage, left object-place memory intact whereas PH ablations (PH-abl), consisting of posterior parahippocampal cortex and para/presubiculum, resulted in an impairment equal to that observed after the combined ablations in the original study. Because the PH ablations invaded the underlying white matter, and because PH lesions made by ibotenic acid (PH-ibo) sparing the underlying fibers resulted in a less severe impairment we suspected that deafferentation of other areas in the medial temporal lobe by transection of rostrally-directed parieto-temporal projections may have contributed to the PH-abl-induced impairment. Recently we investigated the effects on the same object-place task of ibotenic acid lesions of one of the candidate areas for deaffernation, perirhinal cortex. Postoperatively, the animals'average performance decreased from a preoperative baseline of 81% to 74%. This performance was similar to that after the PH-ibo lesions (71%), but significantly better than that after PH-abl lesions (60%). The results suggest that deafferentation of perirhinal cortex by the PH ablations may well have contributed to the severe impairment produced by those ablations, and, more importantly, that one-trial memory for object-place associations depends on both the perirhinal cortex and posterior PH region. 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. Furthermore, a large body of research on humans 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. However, to date it is unknown whether monkeys rely on similar processes to solve recognition memory tasks. To test this possibility, we developed a visual recognition memory paradigm for the rhesus monkey that allowed us to analyze the 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 two 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.

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Project End
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Support Year
53
Fiscal Year
2009
Total Cost
$1,353,439
Indirect Cost
Name
U.S. National Institute of Mental Health
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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
Patai, Eva Zita; Gadian, David G; Cooper, Janine M et al. (2015) Extent of hippocampal atrophy predicts degree of deficit in recall. Proc Natl Acad Sci U S A 112:12830-3
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Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer (2011) Two processes support visual recognition memory in rhesus monkeys. Proc Natl Acad Sci U S A 108:19425-30

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