Changes in memory performance are one of the hallmark symptoms of mild cognitive impairment and are affected by healthy aging as well. Pattern separation, which refers to the process of ...orthogonalizing overlapping inputs into distinct memory representations, may be a sensitive marker of these memory changes. Here, we describe a paradigm, the Behavioral Pattern Separation Task—Object Version (BPS-O task), which reveals age-related changes in pattern separation performance. Specifically, we report an age-related decline in pattern separation in healthy adults, ranging from ages 20 to 89. When we classify those individuals aged 60 and older into two groups, Aged Unimpaired (AU) and Aged Impaired (AI) based on their delayed word recall performance, we observe impairments in pattern separation performance in the Impaired group, but no overall impairment in recognition performance. In contrast, those individuals diagnosed with mild cognitive impairment demonstrate worse performance than age-matched controls in both pattern separation and recognition memory performance. Therefore, the BPS-O task provides a sensitive measure for observing changes in memory performance across the lifespan and may be useful for the early detection of memory impairments that may provide an early signal of later development to mild cognitive impairment.
► Behavioral pattern separation declines in human aging. ► MCI individuals exhibit impairments in both recognition memory and behavioral pattern separation. ► Aged Impaired adults demonstrate pattern separation deficits but normal recognition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Converging data from rodents and humans have demonstrated an age-related decline in pattern separation abilities (the ability to discriminate among similar experiences). Several studies have proposed ...the dentate and CA3 subfields of the hippocampus as the potential locus of this change. Specifically, these studies identified rigidity in place cell remapping in similar environments in the CA3. We used high-resolution fMRI to examine activity profiles in the dentate gyrus and CA3 in young and older adults as stimulus similarity was incrementally varied. We report evidence for "representational rigidity" in older adults' dentate/CA3 that is linked to behavioral discrimination deficits. Using ultrahigh-resolution diffusion imaging, we quantified both the integrity of the perforant path as well as dentate/CA3 dendritic changes and found that both were correlated with dentate/CA3 functional rigidity. These results highlight structural and functional alterations in the hippocampal network that predict age-related changes in memory function and present potential targets for intervention.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest ...that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to linking across species and approaches, and suggest future directions for investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Functional magnetic resonance imaging (fMRI) studies have observed hyperactivity in the hippocampal region in individuals with Mild Cognitive Impairment (MCI). However, the actual source of such ...hyperactivity is not well understood. Studies of aged rats observed similar hyperactive signals in the CA3 region of the hippocampus that correlated with spatial memory deficits and, in particular, with their ability to represent novel environments as being distinct from familiar ones (pattern separation). In this study, we tested the hypothesis that patients with amnestic MCI (aMCI) have deficits in pattern separation, along with hyperactive fMRI BOLD activity in the CA3 region of the hippocampus. We used high-resolution fMRI during a continuous recognition task designed to emphasize pattern separation. We conducted hippocampal subfield-level region of interest analyses to test for dysfunctional activity in aMCI patients. We found that patients showed impaired performance on trials that taxed their pattern separation abilities. We also observed hyperactive BOLD signals in the CA3/dentate and hypoactive signals in the entorhinal cortex during the separation condition. In a high-resolution morphometric analysis of hippocampal subfields, aMCI patients also had smaller CA3/dentate and CA1 volumes (no difference in the subiculum). The CA3/dentate region bilaterally also exhibited the largest shape deformations in aMCI patients, suggesting that this locus is affected early in the course of the disease. These findings suggest that structural and functional changes in the CA3/dentate region of the hippocampus contribute to the deficits in episodic memory that are observed in patients with aMCI. The functional hyperactivity may be evidence for a dysfunctional encoding mechanism, consistent with the predictions of computational models of hippocampal learning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Research efforts in the past two decades have resulted in thousands of potential application areas for nanoparticles - which materials have become industrially relevant? Where are sustainable ...applications of nanoparticles replacing traditional processing and materials? This tutorial review starts with a brief analysis on what makes nanoparticles attractive to chemical product design. The article highlights established industrial applications of nanoparticles and then moves to rapidly emerging applications in the chemical industry and discusses future research directions. Contributions from large companies, academia and high-tech start-ups are used to elucidate where academic nanoparticle research has revolutionized industry practice. A nanomaterial-focused analysis discusses new trends, such as particles with an identity, and the influence of modern instrument advances in the development of novel industrial products.
This tutorial review analyses where nanoparticle research has left the laboratory and today contributes to valuable products.
Abstract Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by constant worry or anxiety over every day life activities and events. The neurobiology of the disorder is ...thought to involve a wide cortical and subcortical network that includes but is not limited to the amygdala and the bed nucleus of the stria terminalis (BNST). These two regions have been hypothesized to play different roles in stress and anxiety; the amygdala is thought to regulate responses to brief emotional stimuli while the BNST is thought to be involved in more chronic regulation of sustained anxiety. In this study, we exposed medication-free GAD patients as well as non-anxious controls to a gambling game where one of the conditions involved non-contingent monetary loss. This condition of high uncertainty was intended to elicit a stressful response and sustained anxiety. Functional MRI scans were collected simultaneously to investigate BOLD activity in the amygdala and BNST during performance of this task. Compared to controls, we found that GAD patients demonstrated decreased activity in the amygdala and increased activity in the BNST. Skin conductance measures showed a consistent early versus late effect within block where GAD patients demonstrated higher arousal than controls late in the task blocks. Based on these results, we hypothesize that GAD patients disengage the amygdala and its response to acute stress earlier than non-anxious controls making way for the BNST to maintain a more sustained response. Future studies are needed to investigate the temporal dynamics of activation and deactivation in these regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper proposes a scheme for adaptive image-contrast enhancement based on a generalization of histogram equalization (HE). HE is a useful technique for improving image contrast, but its effect is ...too severe for many purposes. However, dramatically different results can be obtained with relatively minor modifications. A concise description of adaptive HE is set out, and this framework is used in a discussion of past suggestions for variations on HE. A key feature of this formalism is a "cumulation function," which is used to generate a grey level mapping from the local histogram. By choosing alternative forms of cumulation function one can achieve a wide variety of effects. A specific form is proposed. Through the variation of one or two parameters, the resulting process can produce a range of degrees of contrast enhancement, at one extreme leaving the image unchanged, at another yielding full adaptive equalization.
We use numerical simulations to demonstrate that a source of collimated multi-MeV photons with high conversion efficiency can be achieved using an all-optical single beam setup at an intensity of ...5×10^{22} W/cm^{2} that is already within reach of existing laser facilities. In the studied setup, an unprecedented quasistatic magnetic field (0.4 MT) is driven in a significantly overdense plasma, coupling three key aspects of laser-plasma interactions at high intensities: relativistic transparency, direct laser acceleration, and synchrotron photon emission. The quasistatic magnetic field enhances the photon emission process, which has a profound impact on electron dynamics via radiation reaction and yields tens of TW of directed MeV photons for a PW-class laser.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a ...task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the same spatial locations). Using a standardized test of word recall to divide healthy aged adults into impaired and unimpaired groups relative to young performance, we demonstrate that aged impaired adults are biased away from pattern separation and toward pattern completion, consistent with the rodent studies.
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