Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behavours in rats

Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.

Observed bodies generate object-based spatial codes

Contemporary studies of spatial and social cognition frequently use human figures as stimuli. The interpretation of such studies may be complicated by spatial compatibility effects that emerge when researchers employ spatial responses, and participants spontaneously code spatial relationships about an observed body. Yet, the nature of these spatial codes – whether they are location- or object-based, and coded from the perspective of the observer or the figure – has not been determined. Here, we investigated this issue by exploring spatial compatibility effects arising for objects held by a visually presented whole-bodied schematic human figure. In three experiments, participants responded to the colour of the object held in the figure’s left or right hand, using left or right key presses. Left-right compatibility effects were found relative to the participant’s egocentric perspective, rather than the figure’s. These effects occurred even when the figure was rotated by 90 degrees to the left or to the right, and the coloured objects were aligned with the participant’s midline. These findings are consistent with spontaneous spatial coding from the participant’s perspective and relative to the normal upright orientation of the body. This evidence for object-based spatial coding implies that the domain general cognitive mechanisms that result in spatial compatibility effects may contribute to certain spatial perspective-taking and social cognition phenomena.

The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms

Emerging evidence suggests that a group of dietary-derived phytochemicals known as flavonoids are able to induce improvements in memory, learning and cognition. Flavonoids have been shown to modulate critical neuronal signalling pathways involved in processes of memory, and therefore are likely to affect synaptic plasticity and long-term potentiation mechanisms, widely considered to provide a basis for memory. Animal dietary supplementation studies have further shown that flavonoid-rich foods are able to reverse age-related spatial memory and spatial learning impairments. A more accurate understanding of how a particular spatial memory task works and of which aspects of memory and learning can be assessed in each case, are necessary for a correct interpretation of data relating to diet-cognition experiments. Further understanding of how specific behavioural tasks relate to the functioning of hippocampal circuitry during learning processes might be also elucidative of the specific observed memory improvements. The overall goal of this review is to give an overview of how the hippocampal circuitry operates as a memory system during behavioural tasks, which we believe will provide a new insight into the underlying mechanisms of the action of flavonoids on cognition.

Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats

Rationale: Flavonoid-rich foods have been shown to be able to reverse age-related cognitive deficits in memory and learning in both animals and humans. However, to date, there have been only a limited number of studies investigating the effects of flavonoid-rich foods on cognition in young/healthy animals. Objectives: The aim of this study was to investigate the effects of a blueberry-rich diet in young animals using a spatial working memory paradigm, the delayed non-match task, using an eight-arm radial maze. Furthermore, the mechanisms underlying such behavioural effects were investigated. Results: We show that a 7-week supplementation with a blueberry diet (2 % w/w) improves the spatial memory performance of young rats (2 months old). Blueberry-fed animals also exhibited a faster rate of learning compared to those on the control diet. These behavioural outputs were accompanied by the activation of extracellular signal-related kinase (ERK1/2), increases in total cAMP-response element binding protein (CREB) and elevated levels of pro- and mature brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in hippocampal CREB correlated well with memory performance. Further regional analysis of BDNF gene expression in the hippocampus revealed a specific increase in BDNF mRNA in the dentate gyrus and CA1 areas of hippocampi of blueberry-fed animals. Conclusions: The present study suggests that consumption of flavonoid-rich blueberries has a positive impact on spatial learning performance in young healthy animals, and these improvements are linked to the activation of ERK–CREB– BDNF pathway in the hippocampus.

Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor.

Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods.

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Social isolation in a group living fish impairs cognition

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.

Cognition in context: Evidence on affordances and verbal language

This thesis investigated affordances and verbal language to demonstrate the flexibility of embodied simulation processes. Starting from the assumption that both object/action understanding and language comprehension are tied to the context in which they take place, six studies clarified the factors that modulate simulation. The studies in chapter 4 and 5 investigated affordance activation in complex scenes, revealing the strong influence of the visual context, which included either objects and actions, on compatibility effects. The study in chapter 6 compared the simulation triggered by visual objects and objects names, showing differences depending on the kind of materials processed. The study in chapter 7 tested the predictions of the WAT theory, confirming that the different contexts in which words are acquired lead to the difference typically observed in the literature between concrete and abstract words. The study in chapter 8 on the grounding of abstract concepts tested the mapping of temporal contents on the spatial frame of reference of the mental timeline, showing that metaphoric congruency effects are not automatic, but flexibly mediated by the context determined by the goals of different tasks. The study in chapter 9 investigated the role of iconicity in verbal language, showing sound-to-shape correspondences when every-day object figures, result that validated the reality of sound-symbolism in ecological contexts. On the whole, this evidence favors embodied views of cognition, and supports the hypothesis of a high flexibility of simulation processes. The reported conceptual effects confirm that the context plays a crucial role in affordances emergence, metaphoric mappings activation and language grounding. In conclusion, this thesis highlights that in an embodied perspective cognition is necessarily situated and anchored to a specific context, as it is sustained by the existence of a specific body immersed in a specific environment.

Moving along the mental number line: Interactions between whole-body motion and numerical cognition

Active head turns to the left and right have recently been shown to influence numerical cognition by shifting attention along the mental number line. In the present study, we found that passive whole-body motion influences numerical cognition. In a random-number generation task (Experiment 1), leftward and downward displacement of participants facilitated small number generation, whereas rightward and upward displacement facilitated the generation of large numbers. Influences of leftward and rightward motion were also found for the processing of auditorily presented numbers in a magnitude-judgment task (Experiment 2). Additionally, we investigated the reverse effect of the number-space association (Experiment 3). Participants were displaced leftward or rightward and asked to detect motion direction as fast as possible while small or large numbers were auditorily presented. When motion detection was difficult, leftward motion was detected faster when hearing small number and rightward motion when hearing large number. We provide new evidence that bottom-up vestibular activation is sufficient to interact with the higher-order spatial representation underlying numerical cognition. The results show that action planning or motor activity is not necessary to influence spatial attention. Moreover, our results suggest that self-motion perception and numerical cognition can mutually influence each other.

A BAYESIAN HIERARCHICAL FRAMEWORK FOR SPATIAL MODELING OF fMRI DATA

Functional neuroimaging techniques enable investigations into the neural basis of human cognition, emotions, and behaviors. In practice, applications of functional magnetic resonance imaging (fMRI) have provided novel insights into the neuropathophysiology of major psychiatric,neurological, and substance abuse disorders, as well as into the neural responses to their treatments. Modern activation studies often compare localized task-induced changes in brain activity between experimental groups. One may also extend voxel-level analyses by simultaneously considering the ensemble of voxels constituting an anatomically defined region of interest (ROI) or by considering means or quantiles of the ROI. In this work we present a Bayesian extension of voxel-level analyses that offers several notable benefits. First, it combines whole-brain voxel-by-voxel modeling and ROI analyses within a unified framework. Secondly, an unstructured variance/covariance for regional mean parameters allows for the study of inter-regional functional connectivity, provided enough subjects are available to allow for accurate estimation. Finally, an exchangeable correlation structure within regions allows for the consideration of intra-regional functional connectivity. We perform estimation for our model using Markov Chain Monte Carlo (MCMC) techniques implemented via Gibbs sampling which, despite the high throughput nature of the data, can be executed quickly (less than 30 minutes). We apply our Bayesian hierarchical model to two novel fMRI data sets: one considering inhibitory control in cocaine-dependent men and the second considering verbal memory in subjects at high risk for Alzheimer’s disease. The unifying hierarchical model presented in this manuscript is shown to enhance the interpretation content of these data sets.

Expert-novice Differences in Geologic Field Mapping and Related Cognition

The geosciences are often characterized as a visuospatial field - that is, one in which success depends upon the ability to mentally manipulate, rotate, project, and bend objects. To what extent is the assumption of strong spatial visualization skills among geoscientists correct? This talk will discuss two studies that investigated geoscience expert and novice spatial visualization, both in laboratory experiments and in a novel field study.

Internal Models, Vestibular Cognition, and Mental Imagery: Conceptual Considerations

Vestibular cognition has recently gained attention. Despite numerous experimental and clinical demonstrations, it is not yet clear what vestibular cognition really is. For future research in vestibular cognition, adopting a computational approach will make it easier to explore the underlying mech- anisms. Indeed, most modeling approaches in vestibular science include a top-down or a priori component. We review recent Bayesian optimal observer models, and discuss in detail the conceptual value of prior assumptions, likelihood and posterior estimates for research in vestibular cognition. We then consider forward models in vestibular processing, which are required in order to distinguish between sensory input that is induced by active self-motion, and sensory input that is due to passive self-motion. We suggest that forward models are used not only in the service of estimating sensory states but they can also be drawn upon in an offline mode (e.g., spatial perspective transformations), in which interaction with sensory input is not desired. A computational approach to vestibular cogni- tion will help to discover connections across studies, and it will provide a more coherent framework for investigating vestibular cognition.

UNDERSTANDING NURSE CREATED COGNITIVE ARTIFACTS: PERSONALLY-CREATED-COGNITIVE-ARTIFACTS AS EXTERNAL REPRESENTATIONS OF DISTRIBUTED COGNITION

Manuscript 1: “Conceptual Analysis: Externalizing Nursing Knowledge” We use concept analysis to establish that the report tool nurses prepare, carry, reference, amend, and use as a temporary data repository are examples of cognitive artifacts. This tool, integrally woven throughout the work and practice of nurses, is important to cognition and clinical decision-making. Establishing the tool as a cognitive artifact will support new dimensions of study. Such studies can characterize how this report tool supports cognition, internal representation of knowledge and skills, and external representation of knowledge of the nurse. Manuscript 2: “Research Methods: Exploring Cognitive Work” The purpose of this paper is to describe a complex, cross-sectional, multi-method approach to study of personal cognitive artifacts in the clinical environment. The complex data arrays present in these cognitive artifacts warrant the use of multiple methods of data collection. Use of a less robust research design may result in an incomplete understanding of the meaning, value, content, and relationships between personal cognitive artifacts in the clinical environment and the cognitive work of the user. Manuscript 3: “Making the Cognitive Work of Registered Nurses Visible” Purpose: Knowledge representations and structures are created and used by registered nurses to guide patient care. Understanding is limited regarding how these knowledge representations, or cognitive artifacts, contribute to working memory, prioritization, organization, cognition, and decision-making. The purpose of this study was to identify and characterize the role a specific cognitive artifact knowledge representation and structure as it contributed to the cognitive work of the registered nurse. Methods: Data collection was completed, using qualitative research methods, by shadowing and interviewing 25 registered nurses. Data analysis employed triangulation and iterative analytic processes. Results: Nurse cognitive artifacts support recall, data evaluation, decision-making, organization, and prioritization. These cognitive artifacts demonstrated spatial, longitudinal, chronologic, visual, and personal cues to support the cognitive work of nurses. Conclusions: Nurse cognitive artifacts are an important adjunct to the cognitive work of nurses, and directly support patient care. Nurses need to be able to configure their cognitive artifact in ways that are meaningful and support their internal knowledge representations.