Genetically Determined Hypometabolism in Alzheimer’s Disease and Midlife Risk Factors for Cognitive Impairment

The role of genetic factors in the pathogenesis of Alzheimer’s disease (AD) is not completely understood. In order to improve this understanding, the cerebral glucose metabolism of seven monozygotic and nine dizygotic twin pairs discordant for AD was compared to that of 13 unrelated controls using positron emission tomography (PET). Traditional region of interest analysis revealed no differences between the non-demented dizygotic co-twins and controls. In contrast, in voxel-level and automated region of interest analyses, the non-demented monozygotic co-twins displayed a lower metabolic rate in temporal and parietal cortices as well as in subcortical grey matter structures when compared to controls. Again, no reductions were seen in the non-demented dizygotic co-twins. The reductions seen in the non-demented monozygotic co-twins may indicate a higher genetically mediated risk of AD or genetically mediated hypometabolism possibly rendering them more vulnerable to AD pathogenesis. With no disease modifying treatment available for AD, prevention of dementia is of the utmost importance. A total of 2 165 at least 65 years old twins of the Finnish Twin Cohort with questionnaire data from 1981 participated in a validated telephone interview assessing cognitive function between 1999 and 2007. Those subjects reporting heavy alcohol drinking in 1981 had an elevated cognitive impairment risk over 20 years later compared to light drinkers. In addition, binge drinking was associated with an increased risk even when total alcohol consumption was controlled for, suggesting that binge drinking is an independent risk factor for cognitive impairment. When compared to light drinkers, also non-drinkers had an increased risk of cognitive impairment. Midlife hypertension, obesity and low leisure time physical activity but not hypercholesterolemia were significant risk factors for cognitive impairment. The accumulation of risk factors increased cognitive impairment risk in an additive manner. A previously postulated dementia risk score based on midlife demographic and cardiovascular factors was validated. The risk score was found to well predict cognitive impairment risk, and cognitive impairment risk increased significantly as the score became higher. However, the risk score is not accurate enough for use in the clinic without further testing.

The nature of communication structures of university students in an international web-based computer-supported collaborative learning (CSCL) course

Communication, the flow of ideas and information between individuals in a social context, is the heart of educational experience. Constructivism and constructivist theories form the foundation for the collaborative learning processes of creating and sharing meaning in online educational contexts. The Learning and Collaboration in Technology-enhanced Contexts (LeCoTec) course comprised of 66 participants drawn from four European universities (Oulu, Turku, Ghent and Ramon Llull). These participants were split into 15 groups with the express aim of learning about computer-supported collaborative learning (CSCL). The Community of Inquiry model (social, cognitive and teaching presences) provided the content and tools for learning and researching the collaborative interactions in this environment. The sampled comments from the collaborative phase were collected and analyzed at chain-level and group-level, with the aim of identifying the various message types that sustained high learning outcomes. Furthermore, the Social Network Analysis helped to view the density of whole group interactions, as well as the popular and active members within the highly collaborating groups. It was observed that long chains occur in groups having high quality outcomes. These chains were also characterized by Social, Interactivity, Administrative and Content comment-types. In addition, high outcomes were realized from the high interactive cases and high-density groups. In low interactive groups, commenting patterned around the one or two central group members. In conclusion, future online environments should support high-order learning and develop greater metacognition and self-regulation. Moreover, such an environment, with a wide variety of problem solving tools, would enhance interactivity.

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02).

Longitudinal assessment of neural activity in Parkinson’s disease with mild cognitive impairment using task based fMRI

La maladie de Parkinson (PD) a été uniquement considérée pour ses endommagements sur les circuits moteurs dans le cerveau. Il est maintenant considéré comme un trouble multisystèmique, avec aspects multiples non moteurs y compris les dommages intérêts pour les circuits cognitifs. La présence d’un trouble léger de la cognition (TCL) de PD a été liée avec des changements structurels de la matière grise, matière blanche ainsi que des changements fonctionnels du cerveau. En particulier, une activité significativement réduite a été observée dans la boucle corticostriatale ‘cognitive’ chez des patients atteints de PD-TCL vs. PD non-TCL en utilisant IRMf. On sait peu de cours de ces modèles fonctionnels au fil du temps. Dans cette étude, nous présentons un suivi longitudinal de 24 patients de PD non démente qui a subi une enquête neuropsychologique, et ont été séparés en deux groupes - avec et sans TCL (TCL n = 11, non-TCL n = 13) en fonction du niveau 2 des recommandations de la Movement Disrders Society pour le diagnostic de PD-TCL. Ensuite, chaque participant a subi une IRMf en effectuant la tâche de Wisconsin pendant deux sessions, 19 mois d'intervalle. Nos résultats longitudinaux montrent qu'au cours de la planification de période de la tâche, les patients PD non-TCL engageant les ressources normales du cortex mais ils ont activé en plus les zones corticales qui sont liés à la prise de décision tel que cortex médial préfrontal (PFC), lobe pariétal et le PFC supérieure, tandis que les PD-TCL ont échoué pour engager ces zones en temps 2. Le striatum n'était pas engagé pour les deux groupes en temps 1 et pour le groupe TCL en temps 2. En outre, les structures médiales du lobe temporal étaient au fil du temps sous recrutés pour TCL et Non-TCL et étaient positivement corrélés avec les scores de MoCA. Le cortex pariétal, PFC antérieur, PFC supérieure et putamen postérieur étaient négativement corrélés avec les scores de MoCA en fil du temps. Ces résultats révèlent une altération fonctionnelle pour l’axe ganglial-thalamo-corticale au début de PD, ainsi que des niveaux différents de participation corticale pendant une déficience cognitive. Cette différence de recrutement corticale des ressources pourrait refléter longitudinalement des circuits déficients distincts de trouble cognitive légère dans PD.

Type 2 diabetes; elderly; cognitive deficit; cognitive flexibility; executive functions Resumen

Through meditation, people become aware of what happens in the body and mind, accepting the present experiences as they are and getting a better understanding of the true nature of things. Meditation practices and its inclusion as an intervention technique, have generated great interest in identifying the brain mechanisms through which these practices operate. Different studies suggest that the practice of meditation is associated with the use of different neural networks as well as changes in brain structure and function, represented in higher concentration of gray matter structures at the hippocampus, the right anterior insula, orbital frontal cortex (OFC) and greater involvement of the anterior cingulate cortex (ACC). These and other unrelated studies, shows the multiple implications of the regular practice of mindfulness in the structures and functions of the brain and its relation to certain observable and subjective states in people who practice it. Such evidence enabling the inclusion of mindfulness in psychological therapy where multiple applications have been developed to prove its effectiveness in treating affective and emotional problems, crisis management, social skills, verbal creativity, addiction and craving management, family and caregivers stress of dementia patients and others. However, neuropsychological rehabilitation has no formal proposals for intervention from these findings. The aim of this paper is to propose use of Mindfulness in neuropsychological rehabilitation process, taking the positions and theory of A.R. Luria.

Inverse problems in dynamic cognitive modeling

Inverse problems for dynamical system models of cognitive processes comprise the determination of synaptic weight matrices or kernel functions for neural networks or neural/dynamic field models, respectively. We introduce dynamic cognitive modeling as a three tier top-down approach where cognitive processes are first described as algorithms that operate on complex symbolic data structures. Second, symbolic expressions and operations are represented by states and transformations in abstract vector spaces. Third, prescribed trajectories through representation space are implemented in neurodynamical systems. We discuss the Amari equation for a neural/dynamic field theory as a special case and show that the kernel construction problem is particularly ill-posed. We suggest a Tikhonov-Hebbian learning method as regularization technique and demonstrate its validity and robustness for basic examples of cognitive computations.

Representation in cognitive neuroscience

This article discusses the possible representational nature of two brain cognitive functions: perceptual and executive. Assuming the Newellian definition of representational processes as those that establish an isomorphic relation between two structures, I claim that perceptual processes generate only a partial correspondence (between stimuli properties and brain states) and therefore should not be properly conceived as representational. on the other hand, executive processes encompass the combination of copies (i.e., representations) of perceptual patterns, generating new patterns that subserve behavior. In summary, I criticize the notion of perceptual representations, and propose that brain representational processes are related to executive functions, having a pragmatic dimension.

Conceptual spaces and consciousness: Integrating cognitive and affective processes

In the book Conceptual Spaces: the Geometry of Thought [2000] Peter Gärdenfors proposes a new framework for cognitive science. Complementary to symbolic and subsymbolic [connectionist] descriptions, conceptual spaces are semantic structures constructed from empirical data representing the universe of mental states. We argue that Gärdenfors' modeling can be used in consciousness research to describe the phenomenal conscious world, its elements and their intrinsic relations. The conceptual space approach affords the construction of a universal state space of human consciousness, where all possible kinds of human conscious states could be mapped. Starting from this approach, we discuss the inclusion of feelings and emotions in conceptual spaces, and their relation to perceptual and cognitive states. Current debate on integration of affect/emotion and perception/cognition allows three possible descriptive alternatives: emotion resulting from basic cognition; cognition resulting from basic emotion, and both as relatively independent functions integrated by brain mechanisms. Finding a solution for this issue is an important step in any attempt of successful modeling of natural or artificial consciousness. After making a brief review of proposals in this area, we summarize the essentials of a new model of consciousness based on neuro-astroglial interactions. © 2011 World Scientific Publishing Company.

White matter abnormalities associated with Alzheimer's disease and mild cognitive impairment: A critical review of MRI studies

In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico-cortical and cortico-subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline. © 2013 2013 Expert Reviews Ltd.

Neurobiological Correlates of Apathy in Alzheimer's Disease and Mild Cognitive Impairment: A Critical Review

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

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

Taxonomy development and knowledge representation of nurses' personal cognitive artifacts.

Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive artifacts of other disciplines. Understanding the development and purpose of practitioner's knowledge representations provides important direction to informaticists seeking to create information technology alternatives. The outcome of this paper is to suggest a process template for transition of cognitive artifacts to an information system.

Neural circuits of emotion regulation: a comparison of mindfulness-based and cognitive reappraisal strategies

Dealing with one's emotions is a core skill in everyday life. Effective cognitive control strategies have been shown to be neurobiologically represented in prefrontal structures regulating limbic regions. In addition to cognitive strategies, mindfulness-associated methods are increasingly applied in psychotherapy. We compared the neurobiological mechanisms of these two strategies, i.e. cognitive reappraisal and mindfulness, during both the cued expectation and perception of negative and potentially negative emotional pictures. Fifty-three healthy participants were examined with functional magnetic resonance imaging (47 participants included in analysis). Twenty-four subjects applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level, both strategies were associated with comparable activity of the medial prefrontal cortex and the amygdala. When expecting negative versus neutral stimuli, the mindfulness group showed stronger activations in ventro- and dorsolateral prefrontal cortex, supramarginal gyrus as well as in the left insula. During the perception of negative versus neutral stimuli, the two groups only differed in an increased activity in the caudate in the cognitive group. Altogether, both strategies recruited overlapping brain regions known to be involved in emotion regulation. This result suggests that common neural circuits are involved in the emotion regulation by mindfulness-based and cognitive reappraisal strategies. Identifying differential activations being associated with the two strategies in this study might be one step towards a better understanding of differential mechanisms of change underlying frequently used psychotherapeutic interventions.

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.

Brain structures identification based on feature descriptor

Traumatic Brain Injury -TBI- -1- is defined as an acute event that causes certain damage to areas of the brain. TBI may result in a significant impairment of an individuals physical, cognitive and psychosocial functioning. The main consequence of TBI is a dramatic change in the individuals daily life involving a profound disruption of the family, a loss of future income capacity and an increase of lifetime cost. One of the main challenges of TBI Neuroimaging is to develop robust automated image analysis methods to detect signatures of TBI, such as: hyper-intensity areas, changes in image contrast and in brain shape. The final goal of this research is to develop a method to identify the altered brain structures by automatically detecting landmarks on the image where signal changes and to provide comprehensive information to the clinician about them. These landmarks identify injured structures by co-registering the patient?s image with an atlas where landmarks have been previously detected. The research work has been initiated by identifying brain structures on healthy subjects to validate the proposed method. Later, this method will be used to identify modified structures on TBI imaging studies.