Longitudinal Changes in Functional Brain Connectivity Predicts Conversion to Alzheimer's Disease.

This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy.

Need for Cognitive Closure Modulates How Perceptual Decisions Are Affected by Task Difficulty and Outcome Relevance.

The aim of this study was to assess the extent to which Need for Cognitive Closure (NCC), an individual-level epistemic motivation, can explain inter-individual variability in the cognitive effort invested on a perceptual decision making task (the random motion task). High levels of NCC are manifested in a preference for clarity, order and structure and a desire for firm and stable knowledge. The study evaluated how NCC moderates the impact of two variables known to increase the amount of cognitive effort invested on a task, namely task ambiguity (i.e., the difficulty of the perceptual discrimination) and outcome relevance (i.e., the monetary gain associated with a correct discrimination). Based on previous work and current design, we assumed that reaction times (RTs) on our motion discrimination task represent a valid index of effort investment. Task ambiguity was associated with increased cognitive effort in participants with low or medium NCC but, interestingly, it did not affect the RTs of participants with high NCC. A different pattern of association was observed for outcome relevance; high outcome relevance increased cognitive effort in participants with moderate or high NCC, but did not affect the performance of low NCC participants. In summary, the performance of individuals with low NCC was affected by task difficulty but not by outcome relevance, whereas individuals with high NCC were influenced by outcome relevance but not by task difficulty; only participants with medium NCC were affected by both task difficulty and outcome relevance. These results suggest that perceptual decision making is influenced by the interaction between context and NCC.

Genetic determinants of cognitive responses to caffeine drinking identified from a double-blind, randomized, controlled trial.

The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40mL of either a decaffeinated coffee preparation plus 3mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24h later with the alternative preparation. Cognitive tasks were performed between 30min and 2h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors.

The neural bases for devaluing radical political statements revealed by penetrating traumatic brain injury.

Given the determinant role of ventromedial prefrontal cortex (vmPFC) in valuation, we examined whether vmPFC lesions also modulate how people scale political beliefs. Patients with penetrating traumatic brain injury (pTBI; N = 102) and healthy controls (HCs; N = 31) were tested on the political belief task, where they rated 75 statements expressing political opinions concerned with welfare, economy, political involvement, civil rights, war and security. Each statement was rated for level of agreement and scaled along three dimensions: radicalism, individualism and conservatism. Voxel-based lesion-symptom mapping (VLSM) analysis showed that diminished scores for the radicalism dimension (i.e. statements were rated as less radical than the norms) were associated with lesions in bilateral vmPFC. After dividing the pTBI patients into three groups, according to lesion location (i.e. vmPFC, dorsolateral prefrontal cortex [dlPFC] and parietal cortex), we found that the vmPFC, but not the dlPFC, group had reduced radicalism scores compared with parietal and HC groups. These findings highlight the crucial role of the vmPFC in appropriately valuing political behaviors and may explain certain inappropriate social judgments observed in patients with vmPFC lesions.

Routes of motivation: stable psychological dispositions are associated with dynamic changes in cortico-cortical functional connectivity.

The present study provides a neurobiological framework to the theory of epistemic motivation that has been extensively studied for the last three decades in the domain of social cognition. Epistemic motivations affect the way people generate and validate hypotheses, and ultimately form and modify knowledge. Strong dispositional measures such as need for cognitive closure (NCC), the desire for a quick firm answer (any answer) to a question, show gross and stable inter-individual differences. The cognitive mechanisms and neural underpinnings of such differences, however, remain largely unexplored. Here we show that high (compared to low) levels of NCC, measured with need for cognitive closure scale, are associated with reduced online adjustment in cognitive control, as indexed by behavioral conflict adaptation. This behavioral effect is mediated by dynamic changes in cortico-cortical functional connectivity between prefrontal regions involved in conflict monitoring and implementation of cognitive control. In particular, these regions show increased functional connectivity after exposure to conflict in low but not high NCC individuals. These results demonstrate that the level of flexibility of functional cortico-cortical connections can mediate stable psychological dispositions.