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Abstract Social learning is well established across species. While recent neuroimaging studies show that dorsomedial prefrontal cortex (DMPFC/preSMA) activation correlates with observational learning signals, the precise computations that are implemented by DMPFC/preSMA have remained unclear. To identify whether DMPFC/preSMA supports learning from observed outcomes or observed actions, or possibly encodes even a higher order factor (such as the reliability of the demonstrator), we downregulate DMPFC/preSMA excitability with continuous theta burst stimulation (cTBS) and assess different forms of observational learning. Relative to a vertex-cTBS control condition, DMPFC/preSMA downregulation decreases performance during action-based learning but has no effect on outcome-based learning. Computational modeling reveals that DMPFC/preSMA cTBS disrupts learning the predictability, a proxy of reliability, of the demonstrator and modulates the rate of learning from observed actions. Thus, our results suggest that the DMPFC is causally involved in observational action learning, mainly by adjusting the speed of learning about the predictability of the demonstrator.

Aquest article analitza retrospectivament el discurs que legitima la creació i el desenvolupament de les dues principals institucions actives en el procés de quantificació de la llengua francesa en el món: l’OLG (Observatori de la Llengua Francesa) i l’ODSEF (Observatori Demogràfic i Estadístic de l’Espai Francòfon). L’objectiu d’aquest article és comprendre l’origen d’aquest discurs i com marca la línia d’actuació d’ambdues institucions en escometre la seva missió comuna: la de fer estadístiques sobre la llengua francesa al món. Partint d’un plantejament sociolingüístic crític, l’anàlisi historiogràfica se centra en la documentació generada per ambdues institucions a partir del canvi de mil·lenni, principalment informes analítics o metodològics i publicacions tant acadèmiques i tècniques com enciclopèdiques i “per a tots els públics”. L’anàlisi s’atura en el discurs que tendeix a estructurar el caràcter “objectiu” de la quantificació de la llengua francesa. L’estudi posa en relleu que la construcció d’aquesta objectivitat es basa en arguments polítics alhora que científics que no només emanen de la missió i els principis de l’OIF (Organització Internacional de la Francofonia), sinó també d’altres organismes internacionals com ara l’ONU i la UNESCO. La identificació dels interessos diversos i l’anàlisi de la seva articulació en el discurs permeten observar com determinades tensions polítiques i científiques es veuen neutralitzades com a arguments que situen en el punt de mira la recerca de l’objectivitat a l’hora de posar la llengua francesa en xifres.

Dopamine is thought to play a crucial role in cost-benefit decision making, but so far there is no consensus on the precise role of dopamine in decision making. Here, we review the literature on dopaminergic manipulations of cost-benefit decision making in humans and evaluate how well different theoretical accounts explain the existing body of evidence. Reduced D2 stimulation tends to increase the willingness to bear delay and risk costs (i.e., wait for later rewards, take riskier options), while increased D1 and D2 receptor stimulation increases willingness to bear effort costs. We argue that the empirical findings can best be explained by combining the strengths of two theoretical accounts: in cost-benefit decision making, dopamine may play a dual role both in promoting the pursuit of psychologically close options (e.g., sooner and safer rewards) and in computing which costs are acceptable for a reward at stake. Moreover, we identify several limiting factors in the study designs of previous investigations that prevented a fuller understanding of dopamine’s role in value-based choice. Together, the proposed theoretical framework and the methodological suggestions for future studies may bring us closer to a unifying account of dopamine in healthy and impaired cost-benefit decision making.

Abstract Background Cubital tunnel syndrome is the second most common entrapment neuropathy of the upper extremity. Surgical decompression of the ulnar nerve aims to improve complaints and prevent permanent damage to the nerve. Open and endoscopic release of the cubital tunnel are both used in common practice, but none has proven to be superior. This study assesses patient reported outcome and experience measures (PROMs and PREMs respectively), in addition to objective outcomes of both techniques. Methods A prospective single-center open randomized non-inferiority trial will take place at the Plastic Surgery Department in the Jeroen Bosch Hospital, the Netherlands. 160 patients with cubital tunnel syndrome will be included. Patients are allocated to endoscopic or open cubital tunnel release by randomization. The surgeon and patients are not blinded for treatment allocation. The follow-up time will take 18 months. Discussion Currently, the choice for one of the methods is based on surgeon’s preferences and degree of familiarity with a particular technique. It is assumed that the open technique is easier, faster and cheaper. The endoscopic release, however, has better exposure of the nerve and reduces the chance of damaging the nerve and might decrease scar discomfort. PROMs and PREMs have proven potential to improve the quality of care. Better health care experiences are associated with better clinical outcome in self-reported post-surgical questionnaires. Combining subjective measures with objective outcomes, efficacy, patient treatment experience and safety profile could help differentiating between open and endoscopic cubital tunnel release. This could aid clinicians in evidence based choices towards the best surgical approach in patients with cubital tunnel syndrome. Trial registration This study is registered prospectively with the Dutch Trial Registration under NL9556. Universal Trial Number (WHO-UTN) U1111-1267–3059. Registration date 26–06-2021. The URL: https://www.trialregister.nl/trial/9556

Abstract Processing more likely inputs with higher sensitivity (adaptive coding) enables the brain to represent the large range of inputs coming in from the world. Healthy individuals high in schizotypy show reduced adaptive coding in the reward domain but it is an open question whether these deficits extend to non-motivational domains, such as object categorization. Here, we develop a novel variant of a classic task to test range adaptation for face/house categorization in healthy participants on the psychosis spectrum. In each trial of this task, participants decide whether a presented image is a face or a house. Images vary on a face-house continuum and appear in both wide and narrow range blocks. The wide range block includes most of the face-house continuum (2.50–97.5% face), while the narrow range blocks limit inputs to a smaller section of the continuum (27.5–72.5% face). Adaptive coding corresponds to better performance for the overlapping smaller section of the continuum in the narrow range than in the wide range block. We find that participants show efficient use of the range in this task, with more accurate responses in the overlapping section for the narrow range blocks relative to the wide range blocks. However, we find little evidence that range adaptation in our object categorization task is reduced in healthy individuals scoring high on schizotypy. Thus, reduced range adaptation may not be a domain-general feature of schizotypy.

Analysis of real-time fMRI data from 59 participants undergoing neurofeedback training suggests that reinforcement learning contributes to successful self-regulation in the dopaminergic midbrain.

Theoretical accounts disagree on the role of dopamine in intertemporal choice and assume that dopamine either promotes delay of gratification by increasing the preference for larger rewards or that dopamine reduces patience by enhancing the sensitivity to waiting costs. Here, we reconcile these conflicting accounts by providing empirical support for a novel process model according to which dopamine contributes to two dissociable components of the decision process, evidence accumulation and starting bias. We re-analyzed a previously published data set where intertemporal decisions were made either under the D2 antagonist amisulpride or under placebo by fitting a hierarchical drift diffusion model that distinguishes between dopaminergic effects on the speed of evidence accumulation and the starting point of the accumulation process. Blocking dopaminergic neurotransmission not only strengthened the sensitivity to whether a reward is perceived as worth the delay costs during evidence accumulation (drift rate) but also attenuated the impact of waiting costs on the starting point of the evidence accumulation process (bias). In contrast, re-analyzing data from a D1 agonist study provided no evidence for a causal involvement of D1R activation in intertemporal choices. Taken together, our findings support a novel, process-based account of the role of dopamine for cost-benefit decision making, highlight the potential benefits of process-informed analyses, and advance our understanding of dopaminergic contributions to decision making.

High-resolution rocky intertidal environment and life-history of tropical limpets, as determined by secondary ion mass spectrometry stable oxygen isotopic analysis of modern and historical mollusc shells.

Abstract Mounting evidence has demonstrated that embodied virtual reality, during which physical bodies are replaced with virtual surrogates, can strongly alter cognition and behavior even when the virtual body radically differs from one’s own. One particular emergent area of interest is the investigation of how virtual gender swaps can influence choice behaviors. Economic decision-making paradigms have repeatedly shown that women tend to display more prosocial sharing choices than men. To examine whether a virtual gender swap can alter gender-specific differences in prosociality, 48 men and 51 women embodied either a same- or different-gender avatar in immersive virtual reality. In a between-subjects design, we differentiated between specifically social and non-social decision-making by means of a virtually administered interpersonal and intertemporal discounting task, respectively. We hypothesized that a virtual gender swap would elicit social behaviors that stereotypically align with the gender of the avatar. To relate potential effects to changes in self-perception, we also measured implicit and explicit identification with gendered (or gender-typical) traits prior to and following the virtual experience, and used questionnaires that assessed the strength of the illusion. Contrary to our hypothesis, our results show that participants made less prosocial decisions (i.e., became more selfish) in different-gender avatars, independent of their own biological sex. Moreover, women embodying a male avatar in particular were more sensitive to temptations of immediate rewards. Lastly, the manipulation had no effects on implicit and explicit identification with gendered traits. To conclude, while we showed that a virtual gender swap indeed alters decision-making, gender-based expectancies cannot account for all the task-specific interpersonal and intertemporal changes following the virtual gender swap.

Metacognitive insight into economic preferences has been suggested to enable the consideration of long-term action-consequences. Here, the authors provide a neural link between these phenomena by showing that enhancing frontopolar theta oscillations affects both metacognition and prospective decision making.

Abstract One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known, but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration–exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high-sensitivity C-reactive protein (hsCRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. hsCRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

Despite the popularity of social media, the psychological processes that drive people to engage in it remain poorly understood. The authors applied a computational modeling approach to data from multiple social media platforms to show that engagement can be explained by mechanisms of reward learning.

BackgroundThe importance of menstrual cycle physiology in appetite and obesity is poorly understood. We investigated the effects of body mass index (BMI), menstrual cycle phase and sweet and salty taste on monetary valuation of snack foods.MethodsWe recruited 72 women and after the application of in- and exclusion criteria 31 participants with healthy weight and 25 with obesity remained. The participants completed a willingness to pay (WTP) task to measure subjective value of 30 snack food items in the pre-ovulatory and mid-luteal cycle phases.ResultsGeneralized linear mixed model (GLMM) analysis revealed that BMI, cycle phase and snack taste interacted to influence WTP (−0.15 [−0.22, −0.03], p = 0.002). Hence, WTP was inversely related to BMI, but the strength of the relation depended on cycle phase and taste. The WTP of participants with healthy weight for salty taste changed across cycle phase but the WTP for sweet taste was not affected by cycle phase. Moreover, the cycle effect for the salty snacks ceased in participants with obesity.ConclusionThe inverse effect of BMI on WTP valuation of snack foods contrasts with the positive effect of BMI on pleasantness ratings for milkshakes by the same women that we previously reported. This indicates that the two measures reflect different aspects of food-related valuative processing in obesity. Furthermore, the WTP data suggest that the selection of salty snacks may differ from that of sweet snacks in the pre-ovulatory phase of the menstrual cycle for individuals of healthy weight. The cycle phase does not seem to affect food valuation of participants with obesity. These findings are relevant to understanding and treating obesity in women.

Background: Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms. Objectives: The aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity. Method: A total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation – No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale. Results: Compared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p

Theoretical accounts distinguish between motivational (‘wanting’) and hedonic (‘liking’) dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.

Oxytocin is well-known for its impact on social cognition. This specificity for the social domain, however, has been challenged by findings suggesting a domain-general allostatic function for oxytocin by promoting future-oriented and flexible behavior. In this pre-registered study, we tested the hypothesized domain-general function of oxytocin by assessing the impact of intranasal oxytocin (24 IU) on core aspects of human social (inequity aversion) and non-social decision making (delay of gratification and cognitive flexibility) in 49 healthy volunteers (within-subject design). In intertemporal choice, patience was higher under oxytocin than under placebo, although this difference was evident only when restricting the analysis to the first experimental session (between-group comparison) due to carry-over effects. Further, oxytocin increased cognitive flexibility in reversal learning as well as generosity under conditions of advantageous but not disadvantageous inequity. Our findings show that oxytocin affects both social and non-social decision making, supporting theoretical accounts of domain-general functions of oxytocin.

Studies of neural processes underlying delay of gratification usually focus on prefrontal networks related to curbing affective impulses. Here, we provide evidence for an alternative mechanism that facilitates delaying gratification by mental orientation towards the future. Combining continuous theta-burst stimulation (cTBS) with functional neuroimaging, we tested how the right temporoparietal junction (rTPJ) facilitates processing of future events and thereby promotes delay of gratification. Participants performed an intertemporal decision task and a mental time-travel task in the MRI scanner before and after receiving cTBS over the rTPJ or the vertex (control site). rTPJ cTBS led to both stronger temporal discounting for longer delays and reduced processing of future relative to past events in the mental time-travel task. This finding suggests that the rTPJ contributes to the ability to delay gratification by facilitating mental representation of outcomes in the future. On the neural level, rTPJ cTBS led to a reduction in the extent to which connectivity of rTPJ with striatum reflected the value of delayed rewards, indicating a role of rTPJ-striatum connectivity in constructing neural representations of future rewards. Together, our findings provide evidence that the rTPJ is an integral part of a brain network that promotes delay of gratification by facilitating mental orientation to future rewards.

Decision making requires integrating knowledge gathered from personal experiences with advice from others. The neural underpinnings of the process of arbitrating between information sources has not been fully elucidated. In this study, we formalized arbitration as the relative precision of predictions, afforded by each learning system, using hierarchical Bayesian modeling. In a probabilistic learning task, participants predicted the outcome of a lottery using recommendations from a more informed advisor and/or self-sampled outcomes. Decision confidence, as measured by the number of points participants wagered on their predictions, varied with our definition of arbitration as a ratio of precisions. Functional neuroimaging demonstrated that arbitration signals were independent of decision confidence and involved modality-specific brain regions. Arbitrating in favor of self-gathered information activated the dorsolateral prefrontal cortex and the midbrain, whereas arbitrating in favor of social information engaged the ventromedial prefrontal cortex and the amygdala. These findings indicate that relative precision captures arbitration between social and individual learning systems at both behavioral and neural levels.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.

Generous behaviour increases happiness, but the neural underpinnings of this link are unknown. Here, authors show that promising to be generous changes the neural response in the temporo-parietal junction, and that the connection between this region and the ventral striatum was related to happiness.

Background: Therapeutic inertia (TI) is a common phenomenon among physicians who care for patients with chronic conditions. We evaluated the efficacy of the traffic light system (TLS) educational intervention to reduce TI among neurologists with MS expertise. Methods: In this randomised, controlled trial, 90 neurologists who provide care to MS patients were randomly assigned to the TLS intervention ( n = 45) or to the control group ( n = 45). The educational intervention employed the TLS, a behavioral strategy that facilitates therapeutic choices by facilitating reflective decisions. The TLS consisted in a short, structured, single session intervention of 5-7 min duration. Participants made therapeutic choices of 10 simulated case-scenarios. The primary outcome was a reduction in TI based on a published TI score (case-scenarios in which a participant showed TI divided by the total number of scenarios where TI was possible ranging from 0 to 8). Results: All participants completed the study and were included in the primary analysis. TI was lower in the TLS group (1.47, 95% CI 1.32-1.61) compared to controls (1.93; 95% CI 1.79-2.08). The TLS group had a lower prevalence of TI compared to controls (0.67, 95% CI 0.62-0.71 vs. 0.82, 95% CI 0.78-0.86; p = 0.001). The multivariate analysis, adjusted for age, specialty, years of practice, and risk preference showed a 70% reduction in TI for the TLS intervention compared to controls (OR 0.30; 95% CI 0.10-0.89). Conclusions: In this randomized trial, the TLS strategy decreases the incidence of TI in MS care irrespective of age, expertise, years for training, and risk preference of participants, which would lead to better patient outcomes.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22067-6

The value of rewards arises from multiple hedonic and motivational dimensions. Reward-encoding brain regions such as the ventral striatum (VS) are known to process these dimensions. However, the mechanism whereby distinct reward dimensions are selected for neural processing and guiding behavior remains unclear. Here, we used functional imaging to investigate how human individuals make either hedonic (liking) or motivational (wanting) evaluations of everyday items. We found that the two types of evaluations were differently modulated depending on whether participants won or lost these items. Neural activity in the VS encoded both hedonic and motivational dimensions of reward, whereas ventromedial prefrontal activity encoded primarily motivational evaluations and central orbitofrontal activity encoded predominantly hedonic evaluations. These distinct prefrontal representations arose regardless of which judgment was currently relevant for behavior. Critically, the VS preferentially processed the reward dimension currently being evaluated and showed judgment-specific functional connectivity with the dimension-specific prefrontal areas. Thus, our data are in line with a gating mechanism by which prefrontal cortex (PFC)-VS pathways flexibly encode reward dimensions depending on their behavioral relevance. These findings provide a prototype for a generalized information selection mechanism through content-tailored frontostriatal communication.

Importance: The prescription of generic (non-proprietary) compared to brand-name drugs is increasing worldwide. In many developing and emerging countries, generics companies market products at similar costs as brand-name competitors benefiting from more flexible compliance rules and regulations for marketing their products in the health system. Together, this phenomenon may influence prescriber's behavior (e.g., maintaining the same treatment despite guideline's recommendations or despite evidence of disease progression).Objectives: To compare the prevalence of therapeutic inertia (TI) between primary prescription of brand-name vs. generic drugs in the management of MS in Argentina.Design: We conducted a population-based online study comprising 117 neurologists with expertise in MS. Participants answered questions regarding their clinical practice, most commonly prescribed disease modifying agents, and therapeutic choices of 10 simulated case-scenarios that assessed TI. Inertia was defined as the lack of treatment initiation or escalation despite evidence of clinical and radiological activity (8 case-scenarios, 720 individual responses). We created the generic-brand name score (GBS) according to the 5 most frequently prescribed generic (n = 16) vs. brand-name (n = 9) drugs for MS, where scores higher than 1 indicated higher prescription of generic drugs and scores lower than 1 indicated higher prescription of brand-name agents. Candidate predictors of prescribing generic drugs included demographic data, MS specialist vs. general neurologist, practice setting, years of practice, volume of MS patients, risk preferences, costs of annual treatment.Participants and setting: population-based prospective study using including neurologists who care for patients with multiple sclerosis across Argentina.Exposure: prescription of generic vs. brand-name MS drugsMain outcome of interest: Therapeutic inertia (TI), defined as lack of treatment escalation when goals are unmet. Secondary outcomes included factors associated with generic drug prescription and costs of MS treatment.Results: Ninety participants completed the study (completion rate 76.9%). TI was observed in 153 (21.3%) of participants' responses. The evaluation of aggregate responses revealed a mean GBS score (SD) of 3.44 (2.1), with 46 (51.1%) participants having a GBS equal to or higher than 1. Older age (OR 1.19; 95% CI 1.00–1.42), being a general neurologist (OR 3.91; 95% CI 1.19–12.8), and being more willing to take risks in multiple domains (SOEP score OR 1.06, 95% CI 1.01–1.12) were associated with higher prescription of generic drugs in MS care. Costs of treatment were not associated with prescribing generic drugs. There was no difference in the annual costs of MS treatment for primary prescribers of brand-name vs. generic drugs (67,500 US$ vs. 67,496 US$; p = 0.99).The evaluation of individual responses revealed that participants with higher prescription of generics—reflected by a higher GBS—had higher incident risk of TI (mean GBS 3.61 for TI vs. 2.96 for no TI; p < 0.001). Multivariate analysis revealed that a prescription of generic agents was associated with an increased incident risk of TI (OR 1.56; 95%CI 1.07–2.29). There was no difference in the annual costs of MS treatment for participants that exhibited TI vs. those without TI (67,426 US$ vs. 67,704 US$; p = 0.66).Conclusions: General neurologist, older age, and willingness to take risks were associated with increased prescription of generic drugs despite similar costs compared to brand-name agents. In our study, the prescription of generic-MS drugs was associated with a higher incident risk of therapeutic inertia.

Background: Educational interventions are needed to overcome knowledge-to-action gaps in clinical care. We previously tested the feasibility and potential efficacy of an educational intervention that facilitates treatment decisions in multiple sclerosis care. A demonstration of the usability of such an intervention is crucial prior to demonstration of efficacy in a large trial.Objectives: To evaluate the usability of a novel, pilot-tested intervention aimed at neurologists to improve therapeutic decisions in multiple sclerosis (MS) care.Methods: We surveyed 50 neurologists from Chile, Argentina, and Canada randomized to an educational intervention arm of a pilot feasibility study using the System Usability Score (SUS) to assess the usability of a traffic light system (TLS)-based educational intervention. The TLS facilitates therapeutic decisions, allowing participants to easily recognize high-risk scenarios requiring treatment escalation. The SUS is a validated 10-item questionnaire with five response options. The primary outcome was the average and 95% confidence interval (CI) of the SUS score. Values above 68 are considered highly usable.Results: Of 50 neurologists invited to be part of the study, all completed the SUS scale and the study. For the primary outcome, the average usability score was 74.7 (95%CI 70.1–79.2). There was one outlier with a score of 35. The usability score excluding the outlier was 76.8 (95%CI 72.7–80.8). Multivariate analysis revealed no association between participants' characteristics and the SUS score.Conclusions: Our educational intervention has shown high usability among neurologists. The next step is to evaluate the effectiveness of this educational intervention in facilitating treatment decisions for the management of multiple sclerosis in a large trial.

Microorganisms play a major role in biogeochemical cycles. As such they are attractive candidates for developing new or improving existing biotechnological applications, in order to deal with the accumulation and pollution of organic and inorganic compounds. Their ability to participate in bioremediation processes mainly depends on their capacity to metabolize toxic elements and catalyze reactions resulting in, for example, precipitation, biotransformation, dissolution, or sequestration. The contribution of genomics may be of prime importance to a thorough understanding of these metabolisms and the interactions of microorganisms with pollutants at the level of both single species and microbial communities. Such approaches should pave the way for the utilization of microorganisms to design new, efficient and environmentally sound remediation strategies, as exemplified by the case of arsenic contamination, which has been declared as a major risk for human health in various parts of the world.

BACKGROUND:Negative symptoms are a core feature of schizophrenia and also found in healthy individuals in subclinical forms. According to the current literature the two negative symptom domains, apathy and diminished expression may have different underlying neural mechanisms. Previous observations suggest that striatal dysfunction is associated with apathy in schizophrenia. However, it is unclear whether apathy is specifically related to ventral or dorsal striatal alterations. Here, we investigated striatal dysfunction during reward anticipation in patients with schizophrenia and a non-clinical population, to determine whether it is associated with apathy. METHODS:Chronic schizophrenia patients (n = 16) and healthy controls (n = 23) underwent an event- related functional MRI, while performing a variant of the Monetary Incentive Delay Task. The two negative symptom domains were assessed in both groups using the Brief Negative Symptoms Scale. RESULTS:In schizophrenia patients, we saw a strong negative correlation between apathy and ventral and dorsal striatal activation during reward anticipation. In contrast, there was no correlation with diminished expression. In healthy controls, apathy was not correlated with ventral or dorsal striatal activation during reward anticipation. CONCLUSION:This study replicates our previous findings of a correlation between ventral striatal activity and apathy but not diminished expression in chronic schizophrenia patients. The association between apathy and reduced dorsal striatal activity during reward anticipation suggests that impaired action-outcome selection is involved in the pathophysiology of motivational deficits in schizophrenia.

Background: Diabetes mellitus is a worldwide increasing health problem of which type 2 diabetes is the most prevalent. Previously considered as a problem of industrialised countries, diabetes is currently a huge concern in developing countries and the Democratic Republic of the Congo (DRC) is one of the sub-Saharan countries with a high prevalence rate of diabetes. Deficit of knowledge has already been shown to be one of the barriers preventing diabetic patients from controlling their disease. Objectives: This study aimed to assess the knowledge of type 2 diabetic patients seen at the Institut Médical Evangélique (IME) Kimpese Hospital diabetic clinic, DRC, and the factors associated with their knowledge. Methods: A cross-sectional study involving 184 respondents was conducted at the diabetic clinic of the IME Kimpese Hospital, DRC. We administered a pre-tested questionnaire. Out of a total of 10, scores of < 5, 5 to < 7, and ≥ 7 were classified as ‘poor knowledge’, ‘moderate knowledge’ and ‘good knowledge’, respectively, according to expert consensus. All statistical tests were performed using p < 0.05 as the level of statistical significance. Results: The mean age of respondents was 57.5 years (s.d. ± 1.4, ranging from 40 to 83 years), with 56% being male. The mean diabetes knowledge score was poor: 3.2 out of a total of 10 (s.d. ± 1.7), with the range between 0.2 and 7.7. The majority of respondents (72.3%) had poor general knowledge about diabetes mellitus. Respondents also scored poorly in areas of the causes (35.6%), risk factors (39.3%), clinical features (34.9%), complications (20.5%) and management (42.4%) of diabetes mellitus. Using the student t-test analysis, it was found that age (p = 0.001), gender (p = 0.002), educational level (p = 0.007) and duration of disease (p = 0.032) were significantly associated with poor knowledge of diabetes mellitus. Conclusions: Knowledge of diabetes mellitus among type 2 diabetic patients seen at our setting was poor. Areas of deficiency and factors associated with knowledge of diabetes were identified. Our findings suggest the need for a health education intervention programme for our diabetic patients.

BackgroundPhysicians often do not initiate or intensify treatments when clearly warranted, a phenomenon known as therapeutic inertia (TI). Limited information is available on educational interventions to ameliorate knowledge-to-action gaps in TI.ObjectivesTo evaluate the feasibility and efficacy of an educational intervention compared to usual care among practicing neurologists caring for patients with multiple sclerosis (MS).MethodsWe conducted a pilot double-blind, parallel-group, randomized clinical trial. Inclusion criteria included neurologists who are actively involved in managing MS patients. Participants were exposed to 20 simulated case-scenarios (10 cases at baseline, and 10 cases post-randomization to usual care vs. educational intervention) of relapsing–remitting MS with moderate or high risk of disease progression. The educational intervention employed a traffic light system (TLS) to facilitate decisions, allowing participants to easily recognize high-risk scenarios requiring treatment escalation. We also measured differences between blocks to invoke decision fatigue. The control group responded as they would do in their usual clinical practice not exposed to the educational intervention. The primary feasibility outcome was the proportion of participants who completed the study and the proportion of participants who correctly identified a high-risk case-scenario with the “red traffic light.” Secondary outcomes included decision fatigue (defined as an increment of TI in the second block of case-scenarios compared to the first block) and the efficacy of the educational intervention measured as a reduction in TI for MS treatment.ResultsOf 30 neurologists invited to be part of the study, the participation rate was 83.3% (n = 25). Of the 25 participants, 14 were randomly assigned to the control group and 11 to the intervention group. TI was present in 72.0% of participants in at least one case scenario. For the primary feasibility outcome, the completion rate of the study was 100% (25/25 participants). Overall, 77.4% of participants correctly identified the “red traffic light” for clinical-scenarios with high risk of disease progression. Similarly, 86.4% of participants correctly identified the “yellow traffic light” for cases that would require a reassessment within 6–12 months. For the secondary fatigue outcome, within-group analysis showed a significant increased prevalence of TI in the second block of case-scenarios (decision fatigue) among participants randomized to the control group (TI pre-intervention 57.1% vs. TI post-intervention 71.4%; p = 0.015), but not in the active group (TI pre-intervention 54.6% vs. TI post-intervention 63.6%; p = 0.14). For the efficacy outcome, we found a non-significant reduction in TI for the targeted intervention compared to controls (22.6 vs. 33.9% post-intervention; OR 0.57; 95% CI 0.26–1.22).ConclusionAn educational intervention applying the TLS is feasible and shows some promising results in the identification of high-risk scenarios to reduce decision fatigue and TI. Larger studies are needed to determine the efficacy of the proposed educational intervention.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03134794.

The ability to generalize previously learned information to novel situations is fundamental for adaptive behavior. However, too wide or too narrow generalization is linked to neuropsychiatric disorders. Previous research suggests that interactions between the dopaminergic system and the hippocampus may play a role in generalization, but whether and how the degree of generalization can be modulated via these pathways is currently unknown. Here, we addressed this question in humans using pharmacology, functional magnetic resonance imaging, and computational modeling. Blocking dopamine D2-receptors (D2R) altered generalization behavior as revealed by an increased kurtosis of the generalization gradient, and a decreased width of model-derived generalization parameters. Moreover, D2R-blockade modulated similarity-based responses in the hippocampus and decreased midbrain-hippocampal connectivity, which in turn correlated with individual differences in generalization. These results suggest that dopaminergic activity in the hippocampus may relate to the degree of generalization and highlight a potential target for treatment.

The acid mine drainage (AMD) in Carnoulès (France) is characterized by the presence of toxic metals such as arsenic. Several bacterial strains belonging to the Thiomonas genus, which were isolated from this AMD, are able to withstand these conditions. Their genomes carry several genomic islands (GEIs), which are known to be potentially advantageous in some particular ecological niches. This study focused on the role of the urea island present in the Thiomonas CB2 strain, which carry the genes involved in urea degradation processes. First, genomic comparisons showed that the genome of Thiomonas sp. CB2, which is able to degrade urea, contains a urea genomic island which is incomplete in the genome of other strains showing no urease activity. The urease activity of Thiomonas sp. CB2 enabled this bacterium to maintain a neutral pH in cell cultures in vitro and prevented the occurrence of cell death during the growth of the bacterium in a chemically defined medium. In AMD water supplemented with urea, the degradation of urea promotes iron, aluminium and arsenic precipitation. Our data show that ureC was expressed in situ, which suggests that the ability to degrade urea may be expressed in some Thiomonas strains in AMD, and that this urease activity may contribute to their survival in contaminated environments.

Acid mine drainage (AMD) is a highly toxic environment for most living organisms due to the presence of many lethal elements including arsenic (As). Thiomonas (Tm.) bacteria are found ubiquitously in AMD and can withstand these extreme conditions, in part because they are able to oxidize arsenite. In order to further improve our knowledge concerning the adaptive capacities of these bacteria, we sequenced and assembled the genome of six isolates derived from the Carnoulès AMD, and compared them to the genomes of Tm. arsenitoxydans 3As (isolated from the same site) and Tm. intermedia K12 (isolated from a sewage pipe). A detailed analysis of the Tm. sp. CB2 genome revealed various rearrangements had occurred in comparison to what was observed in 3As and K12 and over 20 genomic islands (GEIs) were found in each of these three genomes. We performed a detailed comparison of the two arsenic-related islands found in CB2, carrying the genes required for arsenite oxidation and As resistance, with those found in K12, 3As, and five other Thiomonas strains also isolated from Carnoulès (CB1, CB3, CB6, ACO3 and ACO7). Our results suggest that these arsenic-related islands have evolved differentially in these closely related Thiomonas strains, leading to divergent capacities to survive in As rich environments.

Apolipoprotein L-I (apoL-I) is present on a subset of HDL particles and is positively correlated with plasma triglycerides (TGs). We measured plasma apoL-I levels in coronary artery disease (CAD) subjects with low HDL who were enrolled in an angiographic CAD prevention trial. At baseline, apoL-I levels (n = 136; range, 2.2–64.1 μg/ml) were right skewed with a large degree of variability. Multivariate analysis for biological determinants of apoL-I revealed that the log of VLDL-TG (+0.17; P < 0.05) and hyperglycemia (HG; +0.26; P < 0.005) independently predicted apoL-I level. Hyperglycemic patients (n = 24) had mean apoL-I levels >50% higher than normoglycemic subjects (n = 112; 13.2 vs. 8.3 μg/ml, respectively; P < 0.001). No relationship between apoL-I level and change in CAD was found (r = 0.06, P = 0.49). Simvastatin-niacin therapy did not alter apoL-I levels (n = 34; P = 0.27), whereas antioxidant vitamins alone increased apoL-I by >50% (n = 36; P < 0.01). Genotyping of a known apoL-I polymorphism (Lys166Glu) did not independently account for any of the variability in apoL-I levels.In conclusion, we found TG and HG to be the strongest predictors of apoL-I within a dyslipidemic CAD population. These data provide further characterization of the novel HDL-associated apoL-I.

Previously we identified and cloned the cDNA for a new protein, apolipoprotein L (apoL), present in plasma and mainly associated with large high density lipoprotein particles. Using 5′ rapid amplification of cDNA ends, RT-PCR and comparison with three Human Genome Project and three expressed sequence tag sequences, we have characterized the gene for apoL and for three additional, highly homologous proteins that constitute a new family of proteins that display no homology with previously described apolipoproteins. The genes for all four proteins, apoL-I, apoL-II, apoL-III, and apoL-IV, are located at chromosome 22q12.1-13.1 within a 127,000-bp region. The apoL-I gene is in the opposite orientation to the other three. All four genes have TATA-less promoters, which contain putative sterol regulatory elements, suggesting that transcription of these genes may be coordinated with that of the low density lipoprotein receptor and genes in pathways involving the synthesis of triglycerides and cholesterol. The gene family has a consensus eight-exon structure with alternative splice sites that could produce as many as eight distinct gene products. The apoL-II and apoL-III genes have alternative transcriptional start sites as a result of additional 5′ exons. apoL-I, apoL-II, and apoL-III are expressed to the highest degree in the lung. Other tissues with high expression are the pancreas, prostate, spleen, liver, and placenta. Four clustered common polymorphisms, three of which altered the protein sequence, were found in apoL-I, all in linkage disequilibrium, and describing two haplotypes: the more common Lys166/Ile244/Lys271 and the rarer Glu166/Met244/Arg271. —Duchateau, P. N., C. R. Pullinger, M. H. Cho, C. Eng, and J. P. Kane. Apolipoprotein L gene family: tissue-specific expression, splicing, promoter regions; discovery of a new gene. J. Lipid Res. 2001. 42: 620–630.

Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The distribution of apoL in normal subjects is asymmetric, with marked skewing toward higher values. No difference was found in apoL concentrations between males and females, but we observed an elevation of apoL in primary hypercholesterolemia (10.1 vs. 8.5 μg/mL in control), in endogenous hypertriglyceridemia (13.8 μg/mL, P < 0.001), combined hyperlipidemia phenotype (18.7 g/mL, P < 0.0001), and in patients with type II diabetes (16.2 μg/mL, P < 0.02) who were hyperlipidemic. Significant positive correlations were observed between apoL and the log of plasma triglycerides in normolipidemia (0.446, P < 0.0001), endogenous hypertriglyceridemia (0.435, P < 0.01), primary hypercholesterolemia (0.66, P < 0.02), combined hyperlipidemia (0.396, P < 0.04), hypoalphalipoproteinemia (0.701, P < 0.005), and type II diabetes with hyperlipidemia (0.602, P < 0.01). Apolipoprotein L levels were also correlated with total cholesterol in normolipidemia (0.257, P < 0.004), endogenous hypertriglyceridemia (0.446, P = 0.001), and non-insulin-dependent diabetes mellitus (NIDDM) (0.548, P < 0.02). No significant correlation was found between apoL and body mass index, age, sex, HDL-cholesterol or fasting glucose and glycohemoglobin levels. ApoL levels in plasma of patients with primary cholesteryl ester transfer protein deficiency significantly increased (7.1 ± 0.5 vs. 5.47 ± 0.27, P < 0.006). —Duchateau, P. N., I. Movsesyan, S. Yamashita, N. Sakai, K-I. Hirano, S. A. Schoenhaus, P. M. O'Connor-Kearns, S. J. Spencer, R. B. Jaffe, R. F. Redberg, B. Y. Ishida, Y. Matsuzawa, J. P. Kane, and M. J. Malloy. Plasma apolipoprotein L concentrations correlate with plasma triglycerides and cholesterol levels in normolipidemic, hyperlipidemic, and diabetic subjects. J. Lipid Res. 2000. 41: 1231–1236.

Probability and risk are important factors for value-based decision making and optimal foraging. In order to survive in an unpredictable world, organisms must be able to assess the probability and risk attached to future events and use this information to generate adaptive behavior. Recent studies in non-human primates and rats have shown that both probability and risk are processed in a distributed fashion throughout the brain at the level of single neurons. Reward probability has mainly been shown to be coded by phasic increases and decreases in firing rates in neurons in the basal ganglia and midbrain. By contrast reward variance is represented in orbitofrontal and posterior cingulate cortex and through the sustained response of dopaminergic midbrain neurons.

Biofilms represent the most common microbial lifestyle, allowing the survival of microbial populations exposed to harsh environmental conditions. Here, we show that the biofilm development of a bacterial species belonging to the Thiomonas genus, frequently found in arsenic polluted sites and playing a key role in arsenic natural remediation, is markedly modified when exposed to subinhibitory doses of this toxic element. Indeed, arsenite [As(III)] exposure led to a considerable impact on biofilm maturation by strongly increasing the extracellular matrix synthesis and by promoting significant cell death and lysis within microcolonies. These events were followed by the development of complex 3D-biofilm structures and subsequently by the dispersal of remobilized cells observed inside the previously formed hollow voids. Our results demonstrate that this biofilm community responds to arsenite stress in a multimodal way, enhancing both survival and dispersal. Addressing this complex bacterial response to As(III) stress, which might be used by other microorganisms under various adverse conditions, may be essential to understand how Thiomonas strains persist in extreme environments.

It is often assumed that decisions are made by rank-ordering and thus comparing the (subjective value of) available choice options. Rank-ordering requires that alternatives are mentally represented at least on an ordinal scale. Because one alternative cannot be at the same time better or worse than another alternative, choices should satisfy transitivity (if alternative A is preferred over B, and B is preferred over C, A should be preferred over C). Yet, individuals often demonstrate striking violations of transitivity (preferring C over A). We used functional magnetic resonance imaging to study the neural correlates of intransitive choices between gambles varying in magnitude and probability of financial gains. Behavioral intransitivities were common. They occurred because participants did not evaluate the gambles independently, but in comparison with the alternative gamble presented. Neural value signals in prefrontal and parietal cortex were not ordinal-scaled and transitive, but reflected fluctuations in the gambles’ local, pairing-dependent preference-ranks. Detailed behavioural analysis of gamble preferences showed that, depending on the difference in the offered gambles’ attributes, participants gave variable priority to magnitude or probability and thus shifted between preferring richer or safer gambles. The variable, context-dependent priority given to magnitude and probability was tracked by insula (magnitude) and posterior cingulate (probability). Their activation-balance may reflect the individual decision rules leading to intransitivities. Thus, the phenomenon of intransitivity is reflected in the organisation of the neural systems involved in risky decision-making.

Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others’ buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants’ decisions arising from the observation of other peoples’ decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision-making and identify a possible neural basis for herd behavior.

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live.

Microbial biotransformations have a major impact on contamination by toxic elements, which threatens public health in developing and industrial countries. Finding a means of preserving natural environments-including ground and surface waters-from arsenic constitutes a major challenge facing modern society. Although this metalloid is ubiquitous on Earth, thus far no bacterium thriving in arsenic-contaminated environments has been fully characterized. In-depth exploration of the genome of the beta-proteobacterium Herminiimonas arsenicoxydans with regard to physiology, genetics, and proteomics, revealed that it possesses heretofore unsuspected mechanisms for coping with arsenic. Aside from multiple biochemical processes such as arsenic oxidation, reduction, and efflux, H. arsenicoxydans also exhibits positive chemotaxis and motility towards arsenic and metalloid scavenging by exopolysaccharides. These observations demonstrate the existence of a novel strategy to efficiently colonize arsenic-rich environments, which extends beyond oxidoreduction reactions. Such a microbial mechanism of detoxification, which is possibly exploitable for bioremediation applications of contaminated sites, may have played a crucial role in the occupation of ancient ecological niches on earth.