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.

The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia.

Background: Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time. Methods: In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after. Results: Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 5580 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.1511.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.0100.316) and 0.294 (0.0550.534), respectively];walnuts with working memory [1.191 (0.0612.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.0060.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.2362.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Rendimiento neuropsicológico y anomalías del cuerpo callosoen adolescentes con antecedentes de prematuridad

Existe una clara relación entre prematuridad y un bajo rendimiento cognitivo y escolar. Sin embargo, los efectos concretos del nacimiento prematuro sobre el funcionamiento cognitivo así como sobre el desarrollo cerebral a largo plazo son poco conocidos. Objetivos: Identificar las disfunciones cognitivas concretas en adolescentes que nacieron prematuros mediante una evaluación neuropsicológica exhaustiva, y relacionar los datos cognitivos con la posible afectación del cuerpo calloso. Metodología y Resultados: se comparó dos muestras de sujetos prematuros y sujetos nacidos a término. Se evaluó el rendimiento cognitivo general y específico, y se cuantificó la estructura cerebral del cuerpo calloso. Se realizaron varios análisis estadísticos y se redactaron diversos artículos presentando los resultados obtenidos. Resultados: adolescentes con antecedentes de prematuridad: a) presentan dificultades cognitivas y anormalidades estructurales, más relacionadas con la edad gestacional que con el peso al nacer; b) tienen déficits cognitivos específicos que pueden explicarse parcialmente por sus disfunciones en el rendimiento cognitivo general; c) la media de sus puntuaciones en el CI se sitúa en el rango normal; d) los subtests de las escalas Wechsler no presentan el mismo grado de sensibilidad; e) presentan una reducción de tamaño del cuerpo calloso, f) más acusada en el genu, posterior midbody y splenium; g) existe una asociación específica entre el genu y el menor rendimiento en funciones del lóbulo prefrontal; h) la edad gestacional presenta una clara relación con las anormalidades del cuerpo calloso y con el bajo rendimiento cognitivo general.

Neuropsicología de los pacientes con síndrome de fibromialgia: relación con dolor y ansiedad

Estudios previos han mostrado la presencia de alteraciones cognitivas en los pacientes con síndrome de fibromialgia (SFM), sin embargo, no han determinado la posible influencia de las distintas variables clínicas en estas alteraciones. El primer objetivo de nuestro estudio es determinar las diferencias en la función cognitiva entre 81 pacientes con SFM y 35 controles sanos mediante una batería de tests neuropsicológicos. El segundo objetivo es determinar la influencia de la ansiedad y el dolor en la función cognitiva en pacientes con SFM. Los resultados de nuestro estudio muestran que las pacientes con SFM desarrollan un rendimiento cognitivo significativamente inferior a los controles sanos en todos los parámetros valorados. El rendimiento neuropsicológico en pacientes con SFM está asociado al dolor, siendo esta relación independiente del nivel de ansiedad. La relación entre el rendimiento cognitivo y la ansiedad también es significativa. Por esta razón, concluimos que el rendimiento cognitivo está principalmente afectado por el dolor, pero además, el nivel de ansiedad explica parte de la variabilidad en los tests neuropsicológicos que no es explicada por el dolor.

Task-induced deactivation from rest extends beyond the default mode brain network

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized"default-mode network" (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.

APOE status modulates the changes in network connectivity induced by brain stimulation in non-demented elders.

Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS. Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Neurocognition in schizophrenia: a study of the productivity and visibility of spanish authors

This paper provides a map of the scientific productivity of authors affiliated to a Spanish institution and who have addressed one of the most important current topics in schizophrenia: The study of cognitive performance. A search of the Web of Science yielded 125 articles that met the inclusion criteria. In order to provide a comprehensive overview of scientific productivity, we examine several bibliometric indicators, concerning both productivity and impact or visibility. The analysis also focuses on qualitative aspects of key theoretical importance, such as the kinds of cognitive functions that are most often assessed and the tests most widely used to evaluate them in clinical practice. The study shows that interest in the subject of cognitive function in schizophrenia has increased considerably in Spain since the beginning of this century. The results also highlight the need to standardize the type of tests to be used in the cognitive assessment of patients with schizophrenia.

Fetal testosterone (2D:4D) as predictor of cognitive reflection

The Cognitive Reflection Test (CRT) is a test introduced by S. Frederick (2005) Cognitive reflection and decision making, J Econ Perspect 19(4): 25-42. The task is designed to measure the tendency to override an intuitive response that is incorrect and to engage in further reflection that leads to the correct response. The consistent sex differences in CRT performance may suggest a role for gonadal hormones, particularly testosterone. A now widely studied putative marker for fetal testosterone is the second-to-fourth digit ratio (2D:4D). This paper tests to what extent 2D:4D, as a proxy for prenatal exposure to testosterone, can predict CRT scores in a sample of 623 students. After controlling for sex, we observe that a lower 2D:4D (reflecting a higher exposure to testosterone) is significantly associated with a higher number of correct answers. The result holds for both hands? 2D:4Ds. In addition, the effect appears to be sharper for females than for males. We also control for patience and math proficiency, which are significantly related to performance in the CRT. But the effect of 2D:4D on performance in CRT is not reduced with these controls, implying that these variables are not mediating the relationship between digit ratio and CRT.

Quality of Learners' Time and Learning Performance Beyond Quantitative Time-on-Task

Peer-reviewed

The role of causal links in performance measurement models

Abstract Purpose: Several well-known managerial accounting performance measurement models rely on causal assumptions. Whilst users of the models express satisfaction and link them with improved organizational performance, academic research, of the realworld applications, shows few reliable statistical associations. This paper provides a discussion on the"problematic" of causality in a performance measurement setting. Design/methodology/approach: This is a conceptual study based on an analysis and synthesis of the literature from managerial accounting, organizational theory, strategic management and social scientific causal modelling. Findings: The analysis indicates that dynamic, complex and uncertain environments may challenge any reliance upon valid causal models. Due to cognitive limitations and judgmental biases, managers may fail to trace correct cause-and-effect understanding of the value creation in their organizations. However, even lacking this validity, causal models can support strategic learning and perform as organizational guides if they are able to mobilize managerial action. Research limitations/implications: Future research should highlight the characteristics necessary for elaboration of convincing and appealing causal models and the social process of their construction. Practical implications: Managers of organizations using causal models should be clear on the purposes of their particular models and their limitations. In particular, difficulties are observed in specifying detailed cause and effect relations and their potential for communicating and directing attention. They should therefore construct their models to suit the particular purpose envisaged. Originality/value: This paper provides an interdisciplinary and holistic view on the issue of causality in managerial accounting models.