Variability in the analysis of a single neuroimaging dataset by many teams.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Thunderstruck: The ACDC model of flexible sequences and rhythms in recurrent neural circuits.

Adaptive sequential behavior is a hallmark of human cognition. In particular, humans can learn to produce precise spatiotemporal sequences given a certain context. For instance, musicians can not only reproduce learned action sequences in a context-dependent manner, they can also quickly and flexibly reapply them in any desired tempo or rhythm without overwriting previous learning. Existing neural network models fail to account for these properties. We argue that this limitation emerges from the fact that sequence information (i.e., the position of the action) and timing (i.e., the moment of response execution) are typically stored in the same neural network weights. Here, we augment a biologically plausible recurrent neural network of cortical dynamics to include a basal ganglia-thalamic module which uses reinforcement learning to dynamically modulate action. This "associative cluster-dependent chain" (ACDC) model modularly stores sequence and timing information in distinct loci of the network. This feature increases computational power and allows ACDC to display a wide range of temporal properties (e.g., multiple sequences, temporal shifting, rescaling, and compositionality), while still accounting for several behavioral and neurophysiological empirical observations. Finally, we apply this ACDC network to show how it can learn the famous "Thunderstruck" song intro and then flexibly play it in a "bossa nova" rhythm without further training.

Signed Reward Prediction Errors in the Ventral Striatum Drive Episodic Memory.

Recent behavioral evidence implicates reward prediction errors (RPEs) as a key factor in the acquisition of episodic memory. Yet, important neural predictions related to the role of RPEs in episodic memory acquisition remain to be tested. Humans (both sexes) performed a novel variable-choice task where we experimentally manipulated RPEs and found support for key neural predictions with fMRI. Our results show that in line with previous behavioral observations, episodic memory accuracy increases with the magnitude of signed (i.e., better/worse-than-expected) RPEs (SRPEs). Neurally, we observe that SRPEs are encoded in the ventral striatum (VS). Crucially, we demonstrate through mediation analysis that activation in the VS mediates the experimental manipulation of SRPEs on episodic memory accuracy. In particular, SRPE-based responses in the VS (during learning) predict the strength of subsequent episodic memory (during recollection). Furthermore, functional connectivity between task-relevant processing areas (i.e., face-selective areas) and hippocampus and ventral striatum increased as a function of RPE value (during learning), suggesting a central role of these areas in episodic memory formation. Our results consolidate reinforcement learning theory and striatal RPEs as key factors subtending the formation of episodic memory.SIGNIFICANCE STATEMENT Recent behavioral research has shown that reward prediction errors (RPEs), a key concept of reinforcement learning theory, are crucial to the formation of episodic memories. In this study, we reveal the neural underpinnings of this process. Using fMRI, we show that signed RPEs (SRPEs) are encoded in the ventral striatum (VS), and crucially, that SRPE VS activity is responsible for the subsequent recollection accuracy of one-shot learned episodic memory associations.

Cognitive Effort Modulates Connectivity between Dorsal Anterior Cingulate Cortex and Task-Relevant Cortical Areas.

Investment of cognitive effort is required in everyday life and has received ample attention in recent neurocognitive frameworks. The neural mechanism of effort investment is thought to be structured hierarchically, with dorsal anterior cingulate cortex (dACC) at the highest level, recruiting task-specific upstream areas. In the current fMRI study, we tested whether dACC is generally active when effort demand is high across tasks with different stimuli, and whether connectivity between dACC and task-specific areas is increased depending on the task requirements and effort level at hand. For that purpose, a perceptual detection task was administered that required male and female human participants to detect either a face or a house in a noisy image. Effort demand was manipulated by adding little (low effort) or much (high effort) noise to the images. Results showed a network of dACC, anterior insula (AI), and intraparietal sulcus (IPS) to be more active when effort demand was high, independent of the performed task (face or house detection). Importantly, effort demand modulated functional connectivity between dACC and face-responsive or house-responsive perceptual areas, depending on the task at hand. This shows that dACC, AI, and IPS constitute a general effort-responsive network and suggests that the neural implementation of cognitive effort involves dACC-initiated sensitization of task-relevant areas.SIGNIFICANCE STATEMENT Although cognitive effort is generally perceived as aversive, its investment is inevitable when navigating an increasingly complex society. In this study, we demonstrate how the human brain tailors the implementation of effort to the requirements of the task at hand. We show increased effort-related activity in a network of brain areas consisting of dorsal anterior cingulate cortex (dACC), anterior insula, and intraparietal sulcus, independent of task specifics. Crucially, we also show that effort-induced functional connectivity between dACC and task-relevant areas tracks specific task demands. These results demonstrate how brain regions specialized to solve a task may be energized by dACC when effort demand is high.

Continuous track paths reveal additive evidence integration in multistep decision making.

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

Context-dependent modulation of cognitive control involves different temporal profiles of fronto-parietal activity.

To efficiently deal with quickly changing task demands, we often need to organize our behaviour on different time scales. For example, to ignore irrelevant and select relevant information, cognitive control might be applied in reactive (short time scale) or proactive (long time scale) mode. These two control modes play a pivotal role in cognitive-neuroscientific theorizing but the temporal dissociation of the underlying neural mechanisms is not well established empirically. In this fMRI study, a cognitive control task was administered in contexts with mainly congruent (MC) and mainly incongruent (MI) trials to induce reactive and proactive control, respectively. Based on behavioural profiles, we expected cognitive control in the MC context to be characterized by transient activity (measured on-trial) in task-relevant areas. In the MI context, cognitive control was expected to be reflected in sustained activity (measured in the intertrial interval) in similar or different areas. Results show that in the MC context, on-trial transient activity (incongruent - congruent trials) was increased in fronto-parietal areas, compared to the MI context. These areas included dorsolateral prefrontal cortex (dlPFC) and intraparietal sulcus (IPS). In the MI context, sustained activity in similar fronto-parietal areas during the intertrial interval was increased, compared to the MC context. These results illuminate how context-dependent reactive and proactive control subtend the same brain areas but operate on different time scales.

Potential Biotechnological Applications of Venoms from the Viperidae Family in Central America for Thrombosis.

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent's total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.

Exploring the behavior of Candida antarctica lipase B in aqueous mixtures of an imidazolium ionic liquid and its surfactant analogue.

The performance of Candida antarctica lipase B (CALB) has been evaluated in 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4)/water mixtures in a wide range of molar fractions (χBMIMBF4) with and without 1-dodecyl-3-methylimidazolium tetrafluoroborate (C12-MIMBF4), a surfactant derived from BMIMBF4. The main aim of this work is to evaluate the influence of χBMIMBF4 over micellar aggregates to assess the activity of enzymatic reactions. The investigated reaction corresponds to the hydrolysis of the substrate p-nitrophenyl laureate in each χBMIMBF4. The kinetic study for χBMIMBF4 at around 0.2 proved to be a border point in enzymatic activity. At χBMIMBF4 = 0.1, the lipase activity increases in the presence of C12-MIMBF4. However, at higher concentrations, BMIMBF4 has a negligible effect over the lipase activity. These results suggest specific interactions between water and BMIMBF4 molecules in relation to CALB. This research highlights the superactivity phenomenon driven by the reaction media and the micelle interface. In this interfacial interaction, BMIMBF4 acts directly on the changes induced on the enzyme upon its interaction with the micellar interface. This study opens a green perspective toward the biocatalysis field.

Pulmonary Valve Reconstruction Using Autologous Pericardium: A Promising Technique to Consider.

Pulmonary valve (PV) surgical treatment is uncommon in adults; however, when it is indicated, replacement with a prosthesis is suggested. Nevertheless, mechanical prostheses have an inherent risk of complications derived from anticoagulation and thrombosis, and biologic prostheses do not have adequate long-term durability. In this context, PV reconstruction surgery emerges as an alternative, avoiding anticoagulation and promising good durability. We present our experience with this procedure in 3 patients with severe PV insufficiency and 1 patient with severe PV stenosis.

A new surgical technique for left atrial reduction in giant left atrium.

Objective: The study objective was to evaluate the safety and clinical and echocardiographic outcomes of a new surgical technique in adult patients diagnosed with a giant left atrium. Methods: We analyzed a cohort of patients who underwent left atrium reduction surgery between January 2016 and June 2020 performed by a specialized surgical team in 2 national reference centers in Lima, Peru. We assessed the major adverse valvular-related events and the New York Heart Association functional class as primary clinical outcomes. Also, our primary echocardiographic endings were the diameter, area, and volume of the left atrium. We assessed these variables at 3 time periods: baseline (t0), perioperative period (t1), and extended follow-up (t2: 12 ± 3.4 months). We carried out descriptive and bivariate exploratory statistical analysis for dependent measures. Results: We included 17 patients, 70.6% of whom were women. Rheumatic mitral valve disease (76.5%) was the main etiology. We performed 14 (82.4%) mitral valve replacements and 3 repairs. Major adverse valvular-related events occurred in 1 patient (5.9%) (hemorrhagic stroke) at t1. A significant reduction in the size of the left atrium was observed: diameter (77 mm vs 48 mm, P < .001), area (75 cm2 vs 31 cm2, P < .001), and volume (332 cm3 vs 90 cm3, P < .001). Compared with t0 and t1, these echocardiographic findings remained without significant changes during t2. Conclusions: Our surgical left atrium reduction technique was associated with improved clinical functionality and reduced left atrium measures in patients with a giant left atrium undergoing mitral valve surgery.

Setting the stage subliminally: unconscious context effects.

An important approach to understand how the brain gives rise to consciousness is to probe the depth of unconscious processing, thus to define the key features that cause conscious awareness. Here, we investigate the possibility for subliminal stimuli to shape the context for unconscious processing. Context effects have generally been assumed to require consciousness. In the present experiment, unconscious context processing was investigated by looking at the impact of the context on the response activation elicited by a subliminal prime. We compared the effects of the same subliminal prime on target processing when the prime was embedded in different unconscious contexts. Results showed that the same prime can evoke opposite responses depending on the unconscious context in which it is presented. Taken together, the results of this study show that context effects can be unconscious.

TiO2 Photocatalyzed Degradation of the Azo Dye Disperse Red 1 in Aqueous Micellar Environments†.

The photoinduced degradation of the azo dye Disperse Red 1 was studied in a microheterogeneous system comprising titanium oxide (TiO2 ) and sodium dodecyl sulfate, exposed to UV light. Degussa P25, Anatase and TiO2 synthesized in acidic conditions were supported on raschig rings. The TiO2 photocatalyzed degradation is enhanced in the vicinity of the surfactant critical micelle value. Further increase on the surfactant concentration leads to a loss in photodegradation performance up to values equivalent to that observed without surfactant. Surfactant influence can be explained by two different phenomena taking place. The increasing concentration of surfactant leads to an increase in micellar concentration, inducing the incorporation of the dye to the hydrophobic moiety of the micelles, rendering the hydroxyl radical unable to interact with the dye. Similarly, the increased concentration of micelles at the photocatalyst/water interface might lead to a decrease in the number of active sites on the TiO2 surface able to either generate reactive species and/or interact with de dye molecules. Additives such as H2 O2 , NaCl, Na2 SO4, and Na2 CO3 are able to override the influence of the surfactant both positively and negatively, being the final outcome of the influence highly dependent on the crystalline form of the TiO2 photocatalyst.

Photocatalytic Degradation of Aqueous Rhodamine 6G Using Supported TiO2 Catalysts. A Model for the Removal of Organic Contaminants From Aqueous Samples.

As a model for the removal of complex organic contaminants from industrial water effluents, the heterogeneous photocatalytic degradation of Rhodamin 6G was studied using TiO2-derived catalysts, incorporated in water as suspension as well as supported in raschig rings. UV and Visible light were tested for the photo-degradation process. TiO2 catalysts were synthesized following acid synthesis methodology and compared against commercial TiO2 catalyst samples (Degussa P25 and Anatase). The bandgap (Eg) of the TiO2 catalysts was determined, were values of 2.97 and 2.98 eV were obtained for the material obtained using acid and basic conditions, respectively, and 3.02 eV for Degussa P25 and 3.18 eV for anatase commercial TiO2 samples. Raschig rings-supported TiO2 catalysts display a good photocatalytic performance when compared to equivalent amounts of TiO2 in aqueous suspension, even though a large surface area of TiO2 material is lost upon support. This is particularly evident by taking into account that the characteristics (XRD, RD, Eg) and observed photodegradative performance of the synthesized catalysts are in good agreement with the commercial TiO2 samples, and that the RH6G photodegradation differences observed with the light sources considered are minimal in the presence of TiO2 catalysts. The presence of additives induce changes in the kinetics and efficiency of the TiO2-catalyzed photodegradation of Rh6G, particularly when white light is used in the process, pointing toward a complex phenomenon, however the stability of the supported photocatalytic systems is acceptable in the presence of the studied additives. In line with this, the magnitude of the chemical oxygen demand, indicates that, besides the different complex photophysical processes taking place, the endproducts of the considered photocatalytic systems appears to be similar.

Copper Recovery From Ammonia Solutions Through Electro-Electrodialysis (EED).

Alkaline leaching with highly selective ammoniacal complexing agents is an interesting alternative for the treatment of copper concentrates. This treatment is beneficial for copper recovery because it allows the formation of soluble amines complexes, with cupric tetramine (  Cu ( NH 3 ) 4 2 + ) being the most stable. In order to suppress the unit operation of solvent extraction (SX) and move directly to the electrochemical process, an electro-electrodialysis (EED) process using ion exchange membranes to obtain copper is proposed. The study contemplates the operation with synthetic ammonia solutions containing copper at different concentrations and current density under standard conditions of pressure and temperature. The presented data demonstrate that the concentration of copper in the solution and the excess of ammonia are inversely related to the efficiency of the current and the voltage of the cell, whereas an increase in current density causes an increase in current efficiency, contrary to what happens in sulfuric systems.

The unfolding action model of initiation times, movement times, and movement paths.

Converging evidence has led to a consensus in favor of computational models of behavior implementing continuous information flow and parallel processing between cognitive processing stages. Yet, such models still typically implement a discrete step between the last cognitive stage and motor implementation. This discrete step is implemented as a fixed decision bound that activation in the last cognitive stage needs to cross before action can be initiated. Such an implementation is questionable as it cannot account for two important features of behavior. First, it does not allow to select an action while withholding it until the moment is appropriate for executing it. Second, it cannot account for recent evidence that cognition is not confined prior to movement initiation, but consistently leaks into movement. To address these two features, we propose a novel neurocomputational model of cognition-action interactions, namely the unfolding action model (UAM). Crucially, the model implements adaptive information flow between the last cognitive processing stage and motor implementation. We show that the UAM addresses the two abovementioned features. Empirically, the UAM accounts for traditional response time data, including positively skewed initiation time distribution, functionally fixed decision bounds and speed-accuracy trade-offs in button-press experimental designs. Moreover, it accounts for movement times, movement paths, and how they are influenced by cognitive-experimental manipulations. This move should close the current gap between abstract decision-making models and behavior observed in natural habitats. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Activation of Electrophile/Nucleophile Pair by a Nucleophilic and Electrophilic Solvation in a SNAr Reaction.

Nucleophilic aromatic substitution reactions of 4-chloroquinazoline toward aniline and hydrazine were used as a model system to experimentally show that a substrate bearing heteroatoms on the aromatic ring as substituent is able to establish intramolecular hydrogen bond which may be activated by the reaction media and/or the nature of the nucleophile.

Task-Relevant Information Modulates Primary Motor Cortex Activity Before Movement Onset.

Monkey neurophysiology research supports the affordance competition hypothesis (ACH) proposing that cognitive information useful for action selection is integrated in sensorimotor areas. In this view, action selection would emerge from the simultaneous representation of competing action plans, in parallel biased by relevant task factors. This biased competition would take place up to primary motor cortex (M1). Although ACH is plausible in environments affording choices between actions, its relevance for human decision making is less clear. To address this issue, we designed an functional magnetic resonance imaging (fMRI) experiment modeled after monkey neurophysiology studies in which human participants processed cues conveying predictive information about upcoming button presses. Our results demonstrate that, as predicted by the ACH, predictive information (i.e., the relevant task factor) biases activity of primary motor regions. Specifically, first, activity before movement onset in contralateral M1 increases as the competition is biased in favor of a specific button press relative to activity in ipsilateral M1. Second, motor regions were more tightly coupled with fronto-parietal regions when competition between potential actions was high, again suggesting that motor regions are also part of the biased competition network. Our findings support the idea that action planning dynamics as proposed in the ACH are valid both in human and non-human primates.

A Natural Deep Eutectic Solvent Formulated to Stabilize ß-Lactam Antibiotics.

ß-lactam antibiotics, such as penicillin share a very unstable chemical structure. In water-based solutions, such as those used for clinical applications, the ß-lactam ring is readily opened due to a nucleophilic or electrophilic attack, leading to the loss of antimicrobial activity. Since the achievement and maintenance of optimum therapeutic levels of ß-lactam antibiotics is critical for the resolution of many infectious clinical situations, and to avoid antibiotic resistance generation, the design of new non-aqueous dosage forms is urgent. Recently, natural deep eutectic solvents (NADES) have emerged as alternative non-toxic and non-aqueous solvents for different biomedical applications. In this work, we formulated and characterized a NADES composed by betaine and urea (BU). Using this solvent, we evaluated the stability of clavulanic acid (CLV) and imipenem (IMP) and characterized their antimicrobial activities calculating the minimal inhibitory concentration. Characterization of BU solvent by infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) indicated that the obtained solvent has a microstructure mainly based on hydrogen bonding interactions and water addition strongly affects its dynamic. The stability of ß-lactam antibiotic IMP and CLV using this solvent was increased by 7 fold and 2.5 fold respectively compared to water when analysed seven days after being dissolved. Microbiological assays showed that antibacterial activity at day seven was significantly decreased for both CLV and IMP when dissolved in water, while no change in their antibacterial properties was observed when antibiotics were dissolved in BU. The increased stability of IMP and CLV in BU may be related to the inert behaviour of the solvent and the higher dynamic restriction that helps antibiotics to maintain a more stable conformation. These data suggest the potential use of BU as a solvent to prevent degradation of ß-lactam antibiotics.

Kinetics of N-glutaryl-L-phenylalanine p-nitroanilide hydrolysis catalyzed by alpha-chymotrypsin in aqueous solutions of alkyltrimethylammonium bromides.

The rate of N-glutaryl-L-phenylalanine p-nitroanilide hydrolysis catalyzed by alpha-chymotripsin has been measured in aqueous solutions of cetyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and dodecyltrimethylammonium bromide at concentrations below and above their critical micellar concentrations (CMC). For the three surfactants considered superactivity was observed, with maximum catalytic efficiencies taking place near the corresponding CMCs. The effect of the surfactants after the CMCs is mostly due to a decreased thermodynamic activity of the substrate due to its incorporation into the micelles. After addition of the surfactants, the Michaelis constant values (corrected to take into account the free substrate concentration) tend to decrease, passing through an ill defined minimum, afterwards reaching a constant value. The catalytic rate constants show the same profiles that the catalytic efficiency, being maxima near the surfactants CMCs. This maximum is more important for the surfactant having the shorter tail. This result is explained by considering that the hydrophobicity of the surfactant influences more the CMC than its association to the enzyme.

Avoiding the conflict: Metacognitive awareness drives the selection of low-demand contexts.

Previous research attempted to explain how humans strategically adapt behavior in order to achieve successful task performance. Recently, it has been suggested that 1 potential strategy is to avoid tasks that are too demanding. Here, we report 3 experiments that investigate the empirically neglected role of metacognitive awareness in this process. In these experiments, participants could freely choose between performing a task in either a high-demand or a low-demand context. Using subliminal priming, we ensured that participants were not aware of the visual stimuli creating these different demand contexts. Our results showed that participants who noticed a difference in task difficulty (i.e., metacognitive aware participants) developed a clear preference for the low-demand context. In contrast, participants who experienced no difference in task difficulty (i.e., metacognitive unaware participants) based their choices on variables unrelated to cognitive demand (e.g., the color or location associated with a context), and did not develop a preference for the low-demand context. Crucially, this pattern was found despite identical task performance in both metacognitive awareness groups. A multiple regression approach confirmed that metacognitive awareness was the main factor driving the preference for low-demand contexts. These results argue for an important role of metacognitive awareness in the strategic avoidance of demanding tasks. (PsycINFO Database Record