Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer's disease

Immunotherapy against amyloid-β(Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer"s disease (AD) models are required. In the aged familiar canine with a Cognitive Dysfunction Syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

Intercultural Competence of Masters of Science in Business Administration and in Technology

Tutkielman tavoitteena on selvittää minkälaista kulttuurienvälistä kompetenssia Lappeenrannan teknillisestä yliopistosta vastavalmistuneilla kauppatieteenmaistereilla sekä diplomi-insinööreillä tulisi olla työnantajien näkökulmasta. Tutkimuksen tarkoituksena on myös tarkastella, että voidaanko kaikkia Lappeenrannan teknillisestä yliopistosta valmistuvia kutsua Kansainvälisiksi Huippuosaajiksi sekä kuinka Lappeenrannan teknillinen yliopisto voisi parantaa vastavalmistuvien kulttuurienvälistä kompetenssia. Teoreettinen osa tarkastelee kulttuurienvälisen kommunikaation tärkeimpiä elementtejä, kulttuurienvälistä kompetenssia ja vastavalmistuneiden kauppatieteenmaistereiden sekä diplomi-insinöörien tarvitsemaa ammatillista osaamista. Empiria koostuu kymmenen työnantajien teemahaastattelun tuloksista. Lopuksi johtopäätöksissä empirian tuloksia verrataan teorian löydöksiin. Tulokset osoittavat että kulttuurienvälinen kompetenssi koostuu kolmesta dimensiosta: henkilökohtaisista ominaisuuksista, tiedosta ja kommunikointikyvystä. Henkilökohtaisiin ominaisuuksiin sisältyvät empaattisuus, epävarmuuden sietokyky sekä avoin ja utelias asenne. Tieto - ulottuvuus koostuu yleisestä ja erityisestä kulttuuritiedosta, kielitaidosta sekä ammatillisesta osaamisesta. Kommunikointikykyyn puolestaan sisältyvät hyvät vuorovaikutustaidot. Työnantajat olettavat nykyään vastavalmistuneilla olevan ammatillisen osaamisen ja kielitaidon lisäksi, kulttuuritietoutta sekä kansainvälistä kokemusta. Lappeenrannan teknillinen yliopisto voisi parantaa vastavalmistuneiden kulttuurienvälistä kompetenssia tarjoamalla kulttuurienvälisen kommunikaation opetusta.

Testing website usability in Spanish-Speaking Academia through heuristic evaluation and cognitive walkthroughs

Although usability evaluations have been focused on assessing different contexts of use, no proper specifications have been addressed towards the particular environment of academic websites in the Spanish-speaking context of use. Considering that this context involves hundreds of millions of potential users, the AIPO Association is running the UsabAIPO Project. The ultimate goal is to promote an adequate translation of international standards, methods and ideal values related to usability in order to adapt them to diverse Spanish-related contexts of use. This article presents the main statistical results coming from the Second and Third Stages of the UsabAIPO Project, where the UsabAIPO Heuristic method (based on Heuristic Evaluation techniques) and seven Cognitive Walkthroughs were performed over 69 university websites. The planning and execution of the UsabAIPO Heuristic method and the Cognitive Walkthroughs, the definition of two usability metrics, as well as the outline of the UsabAIPO Heuristic Management System prototype are also sketched.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects

The ventral striatum / nucleus accumbens has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the nucleus accumbens may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the nucleus accumbens bilaterally. All three had been alcohol dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug related cues. LFPs in the action monitoring task provided further evidence for a role of the nucleus accumbens in goal-directed behaviors. Importantly, alcohol related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the nucleus accumbens and is highly automatic.

Thinking Outside the Box: Enhancing Science Teaching by Combining (Instead of Contrasting) Laboratory and Simulation Activities

The focus of the present work was on 10- to 12-year-old elementary school students’ conceptual learning outcomes in science in two specific inquiry-learning environments, laboratory and simulation. The main aim was to examine if it would be more beneficial to combine than contrast simulation and laboratory activities in science teaching. It was argued that the status quo where laboratories and simulations are seen as alternative or competing methods in science teaching is hardly an optimal solution to promote students’ learning and understanding in various science domains. It was hypothesized that it would make more sense and be more productive to combine laboratories and simulations. Several explanations and examples were provided to back up the hypothesis. In order to test whether learning with the combination of laboratory and simulation activities can result in better conceptual understanding in science than learning with laboratory or simulation activities alone, two experiments were conducted in the domain of electricity. In these experiments students constructed and studied electrical circuits in three different learning environments: laboratory (real circuits), simulation (virtual circuits), and simulation-laboratory combination (real and virtual circuits were used simultaneously). In order to measure and compare how these environments affected students’ conceptual understanding of circuits, a subject knowledge assessment questionnaire was administered before and after the experimentation. The results of the experiments were presented in four empirical studies. Three of the studies focused on learning outcomes between the conditions and one on learning processes. Study I analyzed learning outcomes from experiment I. The aim of the study was to investigate if it would be more beneficial to combine simulation and laboratory activities than to use them separately in teaching the concepts of simple electricity. Matched-trios were created based on the pre-test results of 66 elementary school students and divided randomly into a laboratory (real circuits), simulation (virtual circuits) and simulation-laboratory combination (real and virtual circuits simultaneously) conditions. In each condition students had 90 minutes to construct and study various circuits. The results showed that studying electrical circuits in the simulation–laboratory combination environment improved students’ conceptual understanding more than studying circuits in simulation and laboratory environments alone. Although there were no statistical differences between simulation and laboratory environments, the learning effect was more pronounced in the simulation condition where the students made clear progress during the intervention, whereas in the laboratory condition students’ conceptual understanding remained at an elementary level after the intervention. Study II analyzed learning outcomes from experiment II. The aim of the study was to investigate if and how learning outcomes in simulation and simulation-laboratory combination environments are mediated by implicit (only procedural guidance) and explicit (more structure and guidance for the discovery process) instruction in the context of simple DC circuits. Matched-quartets were created based on the pre-test results of 50 elementary school students and divided randomly into a simulation implicit (SI), simulation explicit (SE), combination implicit (CI) and combination explicit (CE) conditions. The results showed that when the students were working with the simulation alone, they were able to gain significantly greater amount of subject knowledge when they received metacognitive support (explicit instruction; SE) for the discovery process than when they received only procedural guidance (implicit instruction: SI). However, this additional scaffolding was not enough to reach the level of the students in the combination environment (CI and CE). A surprising finding in Study II was that instructional support had a different effect in the combination environment than in the simulation environment. In the combination environment explicit instruction (CE) did not seem to elicit much additional gain for students’ understanding of electric circuits compared to implicit instruction (CI). Instead, explicit instruction slowed down the inquiry process substantially in the combination environment. Study III analyzed from video data learning processes of those 50 students that participated in experiment II (cf. Study II above). The focus was on three specific learning processes: cognitive conflicts, self-explanations, and analogical encodings. The aim of the study was to find out possible explanations for the success of the combination condition in Experiments I and II. The video data provided clear evidence about the benefits of studying with the real and virtual circuits simultaneously (the combination conditions). Mostly the representations complemented each other, that is, one representation helped students to interpret and understand the outcomes they received from the other representation. However, there were also instances in which analogical encoding took place, that is, situations in which the slightly discrepant results between the representations ‘forced’ students to focus on those features that could be generalised across the two representations. No statistical differences were found in the amount of experienced cognitive conflicts and self-explanations between simulation and combination conditions, though in self-explanations there was a nascent trend in favour of the combination. There was also a clear tendency suggesting that explicit guidance increased the amount of self-explanations. Overall, the amount of cognitive conflicts and self-explanations was very low. The aim of the Study IV was twofold: the main aim was to provide an aggregated overview of the learning outcomes of experiments I and II; the secondary aim was to explore the relationship between the learning environments and students’ prior domain knowledge (low and high) in the experiments. Aggregated results of experiments I & II showed that on average, 91% of the students in the combination environment scored above the average of the laboratory environment, and 76% of them scored also above the average of the simulation environment. Seventy percent of the students in the simulation environment scored above the average of the laboratory environment. The results further showed that overall students seemed to benefit from combining simulations and laboratories regardless of their level of prior knowledge, that is, students with either low or high prior knowledge who studied circuits in the combination environment outperformed their counterparts who studied in the laboratory or simulation environment alone. The effect seemed to be slightly bigger among the students with low prior knowledge. However, more detailed inspection of the results showed that there were considerable differences between the experiments regarding how students with low and high prior knowledge benefitted from the combination: in Experiment I, especially students with low prior knowledge benefitted from the combination as compared to those students that used only the simulation, whereas in Experiment II, only students with high prior knowledge seemed to benefit from the combination relative to the simulation group. Regarding the differences between simulation and laboratory groups, the benefits of using a simulation seemed to be slightly higher among students with high prior knowledge. The results of the four empirical studies support the hypothesis concerning the benefits of using simulation along with laboratory activities to promote students’ conceptual understanding of electricity. It can be concluded that when teaching students about electricity, the students can gain better understanding when they have an opportunity to use the simulation and the real circuits in parallel than if they have only the real circuits or only a computer simulation available, even when the use of the simulation is supported with the explicit instruction. The outcomes of the empirical studies can be considered as the first unambiguous evidence on the (additional) benefits of combining laboratory and simulation activities in science education as compared to learning with laboratories and simulations alone.

Gender bias in the Trends in Mathematics and Science Study 2003 (TIMMS) for Canadian students /

This study is a secondary data analysis of the Trends in Mathematics and Science Study 2003 (TIMSS) to determine if there is a gender bias, unbalanced number of items suited to the cognitive skill of one gender, and to compare performance by location. Results of the Grade 8, math portion of the test were examined. Items were coded as verbal, spatial, verbal /spatial or neither and as conventional or unconventional. A Kruskal- Wallis was completed for each category, comparing performance of students from Ontario, Quebec, and Singapore. A Factor Analysis was completed to determine if there were item categories with similar characteristics. Gender differences favouring males were found in the verbal conventional category for Canadian students and in the spatial conventional category for students in Quebec. The greatest differences were by location, as students in Singapore outperformed students from Canada in all areas except for the spatial unconventional category. Finally, whether an item is conventional or unconventional is more important than whether the item is verbal or spatial. Results show the importance of fair assessment for the genders in both the classroom and on standardized tests.

Embodied Autonomy in Digital Ecosystems: From Bio-Inspired Agents to Cognitive Systems

This paper proposes to promote autonomy in digital ecosystems so that it provides agents with information to improve the behavior of the digital ecosystem in terms of stability. This work proposes that, in digital ecosystems, autonomous agents can provide fundamental services and information. The final goal is to run the ecosystem, generate novel conditions and let agents exploit them. A set of evaluation measures must be defined as well. We want to provide an outline of some global indicators, such as heterogeneity and diversity, and establish relationships between agent behavior and these global indicators to fully understand interactions between agents, and to understand the dependence and autonomy relations that emerge between the interacting agents. Individual variations, interaction dependencies, and environmental factors are determinants of autonomy that would be considered. The paper concludes with a discussion of situations when autonomy is a milestone

Evaluation of strategic knowledge of students through authentic tasks of writingin science classroom

The difficulties at evaluating strategic knowledge have been connected to the use of deconxetualized tests that, at the end, do not involve the use of this knowledge. For this reason, an interest in developing authentic writing tasks that offer advantages for these kinds of evaluation have arisen. Throughout this research, authentic writing tasks were developed in a natural sciences class, with the purpose of evaluating the students' strategic knowledge. Different instruments were used to collect data, e.g. Interviews, questionnaires, a self-inform, as well as three samples of writing by the students, with the objective of analyzing the changes that occurred between one and the others, as well as to determine the decisions that students made in order to complete the assigned tasks successfully. An authentic writing task gives great opportunities to evaluate strategic knowledge. These tasks lead students to arrange their knowledge about the topic in hand, organize and adapt it to fit the objectives and the audience, also, it allows them to control and adjust their decisions on the task. This last stage became the perfect opportunity to take notes on the knowledge and regulation of cognitive processes that the students brought into play, as well as to evaluating their understanding of writing and the demands given on the different discursive genres. As a result, the students showed different degrees of strategic knowledge in the task. The students who showed a better strategic knowledge trust in their structural abilities know about discursive genres and have a good performance in basic linguistic abilities. The students who showed weak strategic knowledge distrust their writing skills, seem extremely worried about organizing the content of their texts, fail when checking their writings, and overlook or are unaware of the basic requirements of the discursive genre they are asked to exemplify. It appears that the previous knowledge and experiences at writing the students have been exposed to may affect the strategic knowledge shown when writing in this subject. 

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Individual differences in some (but not all) medial prefrontal regions reflect cognitive demand while regulating unpleasant emotion.

The present study investigated the premise that individual differences in autonomic physiology could be used to specify the nature and consequences of information processing taking place in medial prefrontal regions during cognitive reappraisal of unpleasant pictures. Neural (blood oxygenation level-dependent functional magnetic resonance imaging) and autonomic (electrodermal [EDA], pupil diameter, cardiac acceleration) signals were recorded simultaneously as twenty-six older people (ages 64–66 years) used reappraisal to increase, maintain, or decrease their responses to unpleasant pictures. EDA was higher when increasing and lower when decreasing compared to maintaining. This suggested modulation of emotional arousal by reappraisal. By contrast, pupil diameter and cardiac acceleration were higher when increasing and decreasing compared to maintaining. This suggested modulation of cognitive demand. Importantly, reappraisal-related activation (increase, decrease > maintain) in two medial prefrontal regions (dorsal medial frontal gyrus and dorsal cingulate gyrus) was correlated with greater cardiac acceleration (increase, decrease > maintain) and monotonic changes in EDA (increase > maintain > decrease). These data indicate that these two medial prefrontal regions are involved in the allocation of cognitive resources to regulate unpleasant emotion, and that they modulate emotional arousal in accordance with the regulatory goal. The emotional arousal effects were mediated by the right amygdala. Reappraisal-related activation in a third medial prefrontal region (subgenual anterior cingulate cortex) was not associated with similar patterns of change in any of the autonomic measures, thus highlighting regional specificity in the degree to which cognitive demand is reflected in medial prefrontal activation during reappraisal.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.