Interindividual variability in functional connectivity as long-term correlate of temporal discounting

During intertemporal choice (IT) future outcomes are usually devaluated as a function of the delay, a phenomenon known as temporal discounting (TD). Based on task-evoked activity, previous neuroimaging studies have described several networks associated with TD. However, given its relevance for several disorders, a critical challenge is to define a specific neural marker able to predict TD independently of task execution. To this aim, we used restingstate functional connectivity MRI (fcMRI) and measured TD during economic choices several months apart in 25 human subjects.We further explored the relationship between TD, impulsivity and decision uncertainty by collecting standard questionnaires on individual trait/ state differences. Our findings indicate that fcMRI within and between critical nodes of taskevoked neural networks associated with TD correlates with discounting behavior measured a long time afterwards, independently of impulsivity. Importantly, the nodes form an intrinsic circuit that might support all the mechanisms underlying TD, from the representation of subjective value to choice selection through modulatory effects of cognitive control and episodic prospection

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Geospatial modeling of child mortality across 27 countries in Sub-Saharan Africa

Preventable mortality of children has been targeted as one of the UN’s Sustainable Development Goals for the 2015-30 period. Global decreases in child mortality (4q1) have been seen, although sub-Saharan Africa remains an area of concern, with child mortality rates remaining high relative to global averages or even increasing in some cases. Furthermore, the spatial distribution of child mortality in sub-Saharan Africa is highly heterogeneous. Thus, research that identifies primary risk factors and protective measures in the geographic context of sub-Saharan Africa is needed. In this study, household survey data collected by The Demographic and Health Surveys (DHS) Program aggregated at DHS sub-national area scale are used to evaluate the spatial distribution of child mortality (age 1 to 4) across 27 sub-Saharan Africa countries in relation to a number of demographic and health indicators collected in the DHS surveys. In addition, this report controls for spatial variation in potential environmental drivers of child mortality by modeling it against a suite of geospatial datasets. These datasets vary across the study area in an autoregressive spatial model that accounts for the spatial autocorrelation present in the data. This study shows that socio-demographic factors such as birth interval, stunting, access to health facilities and literacy, along with geospatial factors such as prevalence of Plasmodium falciparum malaria, variety of ethnic groups, mean temperature, and intensity of lights at night can explain up to 60% of the variance in child mortality across 255 DHS sub-national areas in the 27 countries. Additionally, three regions - Western, Central, and Eastern Africa - have markedly different mortality rates. By identifying the relative importance of policy-relevant socio-demographic and environmental factors, this study highlights priorities for research and programs targeting child mortality over the next decade. <br/

A framework to identify structured behavioral patterns within rodent spatial trajectories

Animal behavior is highly structured. Yet, structured behavioral patterns—or “statistical ethograms”—are not immediately apparent from the full spatiotemporal data that behavioral scientists usually collect. Here, we introduce a framework to quantitatively characterize rodent behavior during spatial (e.g., maze) navigation, in terms of movement building blocks or motor primitives. The hypothesis that we pursue is that rodent behavior is characterized by a small number of motor primitives, which are combined over time to produce open-ended movements. We assume motor primitives to be organized in terms of two sparsity principles: each movement is controlled using a limited subset of motor primitives (sparse superposition) and each primitive is active only for time-limited, time-contiguous portions of movements (sparse activity). We formalize this hypothesis using a sparse dictionary learning method, which we use to extract motor primitives from rodent position and velocity data collected during spatial navigation, and successively to reconstruct past trajectories and predict novel ones. Three main results validate our approach. First, rodent behavioral trajectories are robustly reconstructed from incomplete data, performing better than approaches based on standard dimensionality reduction methods, such as principal component analysis, or single sparsity. Second, the motor primitives extracted during one experimental session generalize and afford the accurate reconstruction of rodent behavior across successive experimental sessions in the same or in modified mazes. Third, in our approach the number of motor primitives associated with each maze correlates with independent measures of maze complexity, hence showing that our formalism is sensitive to essential aspects of task structure. The framework introduced here can be used by behavioral scientists and neuroscientists as an aid for behavioral and neural data analysis. Indeed, the extracted motor primitives enable the quantitative characterization of the complexity and similarity between different mazes and behavioral patterns across multiple trials (i.e., habit formation). We provide example uses of this computational framework, showing how it can be used to identify behavioural effects of maze complexity, analyze stereotyped behavior, classify behavioral choices and predict place and grid cell displacement in novel environments

Hippocampal place cells encode global location but not connectivity in a complex space

Flexible navigation relies on a cognitive map of space, thought to be implemented by hippocampal place cells: neurons that exhibit location-specific firing. In connected environments, optimal navigation requires keeping track of one’s location and of the available connections between subspaces. We examined whether the dorsal CA1 place cells of rats encode environmental connectivity in four geometrically identical boxes arranged in a square. Rats moved between boxes by pushing saloon-type doors that could be locked in one or both directions. Although rats demonstrated knowledge of environmental connectivity, their place cells did not respond to connectivity changes, nor did they represent doorways differently from other locations. Place cells coded location in a global reference frame, with a different map for each box and minimal repetitive fields despite the repetitive geometry. These results suggest that CA1 place cells provide a spatial map that does not explicitly include connectivity

A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration.

Both lung disease and elevation of blood glucose are associated with increased glucose concentration (from 0.4 to ~4.0 mM) in the airway surface liquid (ASL). This perturbation of ASL glucose makes the airway more susceptible to infection by respiratory pathogens. ASL is minute (~1 μl/cm(2)) and the measurement of glucose concentration in the small volume ASL is extremely difficult. Therefore, we sought to develop a fluorescent biosensor with sufficient sensitivity to determine glucose concentrations in ASL in situ. We coupled a range of environmentally sensitive fluorophores to mutated forms of a glucose/galactose-binding protein (GBP) including H152C and H152C/A213R and determined their equilibrium binding properties. Of these, GBP H152C/A213R-BADAN (Kd 0.86 ± 0.01 mM, Fmax/F0 3.6) was optimal for glucose sensing and in ASL increased fluorescence when basolateral glucose concentration was raised from 1 to 20 mM. Moreover, interpolation of the data showed that the glucose concentration in ASL was increased, with results similar to that using glucose oxidase analysis. The fluorescence of GBP H152C/A213R-BADAN in native ASL from human airway epithelial cultures in situ was significantly increased over time when basolateral glucose was increased from 5 to 20 mM. Overall our data indicate that this GBP is a useful tool to monitor glucose homoeostasis in the lung

Mapping poverty using mobile phone and satellite data

Poverty is one of the most important determinants of adverse health outcomes globally, a major cause of societal instability and one of the largest causes of lost human potential. Traditional approaches to measuring and targeting poverty rely heavily on census data, which in most low- and middle-income countries (LMICs) are unavailable or out-of-date. Alternate measures are needed to comp- lement and update estimates between censuses. This study demonstrates how public and private data sources that are commonly available for LMICs can be used to provide novel insight into the spatial distribution of poverty. We evalu- ate the relative value of modelling three traditional poverty measures using aggregate data from mobile operators and widely available geospatial data. Taken together, models combining these data sources providethebest predictive power (highest r 2 ¼ 0.78) and lowest error, but generally models employing mobile data only yield comparable results, offering the potential to measure poverty more frequently and at finer granularity. Stratifying models into urban and rural areas highlights the advantage of using mobile data in urban areas and different data in different contexts. The findings indicate the possibility to estimate and continually monitor poverty rates at high spatial resolution in countries with limited capacity to support traditional methods of datacollection

Neural processes mediating contextual influences on human choice behaviour

Contextual influences on choice are ubiquitous in ecological settings. Current evidence suggests that subjective values are normalized with respect to the distribution of potentially available rewards. However, how this context-sensitivity is realised in the brain remains unknown. To address this, here we examine functional magnetic resonance imaging (fMRI) data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts. At the beginning of each block (when information about context is provided), hippocampus is activated and this response is enhanced when contextual influence on choice increases. In addition, response to value in ventral tegmental area/substantia nigra (VTA/SN) shows context-sensitivity, an effect enhanced with an increased contextual influence on choice. Finally, greater response in hippocampus at block start is associated with enhanced context sensitivity in VTA/SN. These findings suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection