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Moustafa A.A.,University of Western Sydney | Hewedi D.H.,Ain Shams University | Eissa A.M.,Ain Shams University | Myers C.E.,Rutgers University | And 2 more authors.
PLoS ONE | Year: 2012

Previous studies have shown that high total homocysteine levels are associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). In this study, we test the relationship between cognitive function and total homocysteine levels in healthy subjects (Global Dementia Rating, CDR = 0) and individuals with MCI (CDR = 0.5). We have used a cognitive task that tests learning and generalization of rules, processes that have been previously shown to rely on the integrity of the striatal and hippocampal regions, respectively. We found that total homocysteine levels are higher in MCI individuals than in healthy controls. Unlike what we expected, we found no difference between MCI subjects and healthy controls in learning and generalization. We conducted further analysis after diving MCI subjects in two groups, depending on their Global Deterioration Scale (GDS) scores: individuals with very mild cognitive decline (vMCD, GDS = 2) and mild cognitive decline (MCD, GDS = 3). There was no difference among the two MCI and healthy control groups in learning performance. However, we found that individuals with MCD make more generalization errors than healthy controls and individuals with vMCD. We found no difference in the number of generalization errors between healthy controls and MCI individuals with vMCD. In addition, interestingly, we found that total homocysteine levels correlate positively with generalization errors, but not with learning errors. Our results are in agreement with prior results showing a link between hippocampal function, generalization performance, and total homocysteine levels. Importantly, our study is perhaps among the first to test the relationship between learning (and generalization) of rules and homocysteine levels in healthy controls and individuals with MCI. © 2012 Moustafa et al.

McAuley J.D.,Michigan State University | McAuley J.D.,Stress and Motivated Behavior Institute | Miller J.P.,Ohio Valley University | Wang M.,University of Maryland University College | And 2 more authors.
Experimental Aging Research | Year: 2010

This article examines age differences in individual's ability to produce the durations of learned auditory and visual target events either in isolation (focused attention) or concurrently (divided attention). Young adults produced learned target durations equally well in focused and divided attention conditions. Older adults, in contrast, showed an age-related increase in timing variability in divided attention conditions that tended to be more pronounced for visual targets than for auditory targets. Age-related impairments were associated with a decrease in working memory span; moreover, the relationship between working memory and timing performance was largest for visual targets in divided attention conditions. © Taylor & Francis Group, LLC.

Somlai Z.,Semmelweis University | Moustafa A.A.,Rutgers University | Keri S.,National Psychiatry Center | Keri S.,University of Szeged | And 3 more authors.
Schizophrenia Research | Year: 2011

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n = 40) performed similarly to healthy controls (n = 30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia. © 2010.

Krishna R.,The New School | Moustafa A.A.,Rutgers University | Moustafa A.A.,University of Western Sydney | Eby L.A.,Bridgewater College | And 4 more authors.
Cognitive and Behavioral Neurology | Year: 2012

Damage to the hippocampal and frontostriatal systems can occur across the adult life span. As these 2 systems are involved in learning processes, mild impairments of learning and generalization might be observed even in healthy aging. In this study, we examined both learning and generalization performance in 3 groups of older adults: young-older (ages 45 to 60 y), middle-older (ages 61 to 75 y), and oldest-older (ages 76 to 90 y). We used a simple computerized concurrent discrimination task in which the learning phase has shown sensitivity to frontostriatal dysfunction, and the generalization phase to hippocampal damage. We found that age significantly affected initial learning performance, but generalization was spared in all but the oldest group, with some individuals still generalizing very well. This finding suggests that (a) learning abilities are affected in healthy aging (consistent with earlier reports of frontostriatal dysfunction in healthy aging) and (b) generalization deficit does not necessarily occur in early older age. We hypothesize that generalization deficits in some in the oldest group may be related to hippocampal pathology. Our data shed light on possible neural system dysfunction in healthy aging and Alzheimer disease. Copyright © 2012 by Lippincott Williams & Wilkins.

Montgomery K.S.,Texas A&M University | Edwards G.,University of Texas Health Science Center at Houston | Levites Y.,University of Florida | Kumar A.,University of Florida | And 5 more authors.
Hippocampus | Year: 2016

Elevated β-amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the "transfer" of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative "transfer learning" task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APPswePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β-amyloid-induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg-SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal-dependent learning may be useful for early identification of AD-like pathology. © 2015 Wiley Periodicals, Inc.

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