Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning

Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words

Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n -back working memory paradigm

Purpose: Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with 99mTc-HMPAO using low irradiation dose. Materials and methods: A two-scans protocol was applied to 12 healthy young volunteers using 270MBq of 99mTc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal n-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. Results: Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and 15O-PET studies. Conclusion: The results support the use of 99mTc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical population

Individual differences in cognitive plasticity: an investigation of training curves in younger and older adults

To date, cognitive intervention research has provided mixed but nevertheless promising evidence with respect to the effects of cognitive training on untrained tasks (transfer). However, the mechanisms behind learning, training effects and their predictors are not fully understood. Moreover, individual differences, which may constitute an important factor impacting training outcome, are usually neglected. We suggest investigating individual training performance across training sessions in order to gain finer-grained knowledge of training gains, on the one hand, and assessing the potential impact of predictors such as age and fluid intelligence on learning rate, on the other hand. To this aim, we propose to model individual learning curves to examine the intra-individual change in training as well as inter-individual differences in intra-individual change. We recommend introducing a latent growth curve model (LGCM) analysis, a method frequently applied to learning data but rarely used in cognitive training research. Such advanced analyses of the training phase allow identifying factors to be respected when designing effective tailor-made training interventions. To illustrate the proposed approach, a LGCM analysis using data of a 10-day working memory training study in younger and older adults is reported

Coordinated within-Trial Dynamics of Low-Frequency Neural Rhythms Controls Evidence Accumulation

Higher cognitive functions, such as human perceptual decision making, require information processing and transmission across widespread cortical networks. Temporally synchronized neural firing patterns are advantageous for efficiently representing and transmitting information within and between assemblies. Computational, empirical, and conceptual considerations all lead to the expectation that the informational redundancy of neural firing rates is positively related to their synchronization. Recent theorizing and initial evidence also suggest that the coding of stimulus characteristics and their integration with behavioral goal states require neural interactions across a hierarchy of timescales. However, most studies thus have focused on neural activity in a single frequency range or on a restricted set of brain regions. Here we provide evidence for cooperative spatiotemporal dynamics of slow and fast EEGsignals during perceptual decision making at the single-trial level. Participants performed three masked two-choice decision tasks, one each with numerical, verbal, or figural content. Decrements in posterior power (8 -14 Hz) were paralleled by increments in high-frequency (>30 Hz) signal entropy in trials demanding active sensory processing. Simultaneously, frontocentral power (4 -7 Hz) increased, indicating evidence integration. The coordinated a/0 dynamics were tightly linked to decision speed and remarkably similar across tasks, suggesting a domain-general mechanism. In sum, we demonstrate an inverse association between decision-related changes in widespread low-frequency power and local high-frequency entropy. The cooperation among mechanisms captured by these changes enhances the informational density of neural response patterns and qualifies as a neural coding system in the service of perceptual decision making

Human Aging Magnifies Genetic Effects on Executive Functioning and Working Memory

We demonstrate that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. We assess two common Val/Met polymorphisms, one affecting the Catechol-O-Methyltransferase (COMT) enzyme, which degrades dopamine (DA) in prefrontal cortex (PFC), and the other influencing the brain-derived neurotrophic factor (BDNF) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of COMT genotype on cognitive performance are magnified in old age and modulated by BDNF genotype. Older COMT Val homozygotes showed particularly low levels of performance if they were also BDNF Met carriers. The age-associated magnification of COMT gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in PFC to cognitive performance. The modulation of COMT effects by BDNF extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe

INTRODUCTION Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond

Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm

{Purpose} Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with 99mTc-HMPAO using low irradiation dose. {Materials and methods} A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of 99mTc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal {n}-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. {Results} Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and 15O-PET studies. {Conclusion} The results support the use of 99mTc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations

Transitions dans le parcours de vie et construction des inégalités

Tout au long de leur existence, les individus suivent des chemins singuliers dont les trajectoires ne sont pas le simple fait de la seule volonté ou du hasard. Ces cheminements se révèlent souvent générateurs d'inégalités entre individus, notamment au cours des transitions des âges de la vie (enfance, adolescence, âge adulte, grand âge), ou lors de différentes étapes (mariage, divorce, deuil, etc). C'est afin de mieux comprendre les modalités et les combinaisons d'influence à l'origine des inégalités dans les parcours de vie, que les éditeurs de cet ouvrage ont réuni des chercheurs issus des sciences psychologiques, sociales et économiques, afin de croiser leurs regards sur la manière dont ces inégalités se creusent ou se réduisent au fil des trajectoires. Cet ouvrage interdisciplinaire met en relief la richesse d'une approche des inégalités dans la perspective dynamique du parcours de vie.Peer reviewe

Contrôle exécutif et réseaux neurofonctionnels au cours du vieillissement normal : un test de l'hypothèse de dé-différenciation cognitive

Ce travail examine l'hypothèse de dé-différentiation cognitive (ou augmentation des corrélations entre capacités cognitives avec l'âge) en transférant celle-ci au niveau de l'activité cérébrale et des associations qu'entretiennent les aires préfrontales avec d'autres structures. Les données comportementales mettent en évidence, du moins partiellement, une augmentation des corrélations chez les adultes âgés, entre performances de vitesse de traitement, inhibition, mémoire de travail et raisonnement. Les données cérébrales, obtenues lors de la réalisation d'épreuves de mémoire de travail, suggèrent que les âgés présentent une activité plus diffuse dans les aires préfrontales, mais aussi les régions plus postérieures (notamment occipitales). Ces changements d'activité impliquent en outre une modification des associations entre ces structures en faveur d'une compensation fonctionnelle. Nous suggérons que la dé-différentiation repose sur un besoin croissant de compensation avec l'âge, voire d'une majeure coopération entre des processus qui ont été plus indépendants durant l'adolescence et le début de l'âge adulte

Développement intellectuel au cours du cycle de vie : sources de variabilité et niveaux d’analys

Intellectual development across the lifespan: Sources of variability and levels of analysis In the past, research on lifespan changes in intelligence has regarded variability primarily as an outcome of development. Here, we argue that it may also function as an agent of ontogenetic changes in cognitive functioning. We first review the conceptual and methodological status of variability in psychometric, experimental, and neuroscience approaches to cognitive aging. We then suggest that neural network models are suitable tools for exploring the hypothesis that variability acts as an agent of developmental changes. According to a computational model of lifespan changes in dopaminergic neuromodulation, neural and cognitive senescence can be characterized by a developmental cascade of less distinct neuronal signaling, less separable processing pathways, and less differentiated cerebral representations. Of particular interest in this cascade are interactions between external input noise and senescent increments in endogenous neuronal noise. We stress the need to promote integrative theorizing about behavioral senescence across neural and cognitive levels of analysis.La variabilité a longtemps été considérée comme une conséquence du développement intellectuel au cours du cycle de vie. Nous soutenons dans cet article que la variabilité elle-même peut servir de vecteur potentiel des changements ontogénétiques dans le fonctionnement cognitif. D’abord, nous examinerons le statut conceptuel et méthodologique de la variabilité dans les approches psychométrique, expérimentale et des neurosciences du vieillissement cognitif. Nous proposerons ensuite que les modèles de neurones formels constituent des outils appropriés dans l’exploration de la variabilité en tant qu’agent du changement développemental. Selon un modèle computationnel des modifications de la neuromodulation dopaminergique durant le cycle de vie, la sénescence neuronale et cognitive peut être caractérisée par une cascade d’événements tels qu’une moindre discriminabilité du signal neuronal, une moindre distinctivité des voies de traitement et une moindre différenciation des représentations cérébrales. Dans cette cascade développementale, les interactions entre le bruit externe et l’accroissement du bruit neuronal endogène lié à la sénescence présentent un intérêt particulier. Nous insisterons sur la nécessité de promouvoir une théorisation unifiée du vieillissement comportemental aux niveaux d’analyse neuronal et cognitif.Chicherio Christian, Lindenberger Ulman. Développement intellectuel au cours du cycle de vie : sources de variabilité et niveaux d’analys. In: L'année psychologique. 2008 vol. 108, n°4. pp. 757-793