Independent neural computation of value from other people's confidence

Expectation of reward can be shaped by the observation of actions and expressions of other people in one's environment. A person's apparent confidence in the likely reward of an action, for instance, makes qualities of their evidence, not observed directly, socially accessible. This strategy is computationally distinguished from associative learning methods that rely on direct observation, by its use of inference from indirect evidence. In twenty-three healthy human subjects, we isolated effects of first-hand experience, other people's choices, and the mediating effect of their confidence, on decision-making and neural correlates of value within ventromedial prefrontal cortex (vmPFC). Value derived from first hand experience and other people's choices (regardless of confidence) were indiscriminately represented across vmPFC. However, value computed from agent choices weighted by their associated confidence was represented with specificity for ventromedial area 10. This pattern corresponds to shifts of connectivity and overlapping cognitive processes along a posterior-anterior vmPFC axis. Task behavior and self-reported self-reliance for decision-making in other social contexts correlated. The tendency to conform in other social contexts corresponded to increased activation in cortical regions previously shown to respond to social conflict in proportion to subsequent conformity (Campbell-Meiklejohn et al., 2010). The tendency to self-monitor predicted a selectively enhanced response to accordance with others in the right temporoparietal junction (rTPJ). The findings anatomically decompose vmPFC value representations according to computational requirements and provide biological insight into the social transmission of preference and reassurance gained from the confidence of others. Significance Statement: Decades of research have provided evidence that the ventromedial prefrontal cortex (vmPFC) signals the satisfaction we expect from imminent actions. However, we have a surprisingly modest understanding of the organization of value across this substantial and varied region. This study finds that using cues of the reliability of other peoples'; knowledge to enhance expectation of personal success generates value correlates that are anatomically distinct from those concurrently computed from direct, personal experience. This suggests that representation of decision values in vmPFC is suborganized according to the underlying computation, consistent with what we know about the anatomical heterogeneity of the region. These results also provide insight into the observational learning process by which someone else's confidence can sway and reassure our choices

In for a penny, in for a pound: methylphenidate reduces the inhibitory effect of high stakes on persistent risky choice

Methylphenidate (MPH) is a stimulant that increases extracellular levels of dopamine and noradrenaline. It can diminish risky decision-making tendencies in certain clinical populations. MPH is also used, without license, by healthy adults, but the impact on their decision-making is not well established. Previous work has found that dopamine receptor activity of healthy adults can modulate the influence of stake magnitude on decisions to persistently gamble after incurring a loss. In this study, we tested for modulation of this effect by MPH in 40 healthy human adults. In a double-blind experiment, 20 subjects received 20 mg of MPH, while 20 matched controls received a placebo. All were provided with 30 rounds of opportunities to accept an incurred loss from their assets or opt for a "double-or-nothing" gamble that would either avoid or double it. Rounds began with a variable loss that would double with every failed gamble until it was accepted, recovered, or reached a specified maximum. Probability of recovery on any gamble was low and ambiguous. Subjects receiving placebo gambled less as the magnitude of the stake was raised and as the magnitude of accumulated loss escalated over the course of the task. In contrast, subjects treated with MPH gambled at a consistent rate, well above chance, across all stakes and trials. Trait reward responsiveness also reduced the impact of high stakes. The findings suggest that elevated catecholamine activity by MPH can disrupt inhibitory influences on persistent risky choice in healthy adults

Hyper- and hypo-mentalizing in patients with first-episode schizophrenia: fMRI and behavioural studies

Background: Historically, research investigating neural correlates of mentalizing deficits in schizophrenia has focused on patients who have been ill for several years with lengthy exposure to medication. Little is known about the neural and behavioural presentations of theory-of-mind deficits in schizophrenia, shortly after the first episode of psychosis. Methods: We investigated social cognition in seventeen recently diagnosed first-episode schizophrenia (FES) patients with little or no exposure to antipsychotic medication and 1:1 matched healthy controls. We recorded behavioural and neural responses to the Animated Triangles Task (ATT), which is a non-verbal validated mentalizing task that measures the ascription of intentionality to the movements of objects. Results: FES patients under-interpreted social cues and over-interpreted non-social cues. These effects were influenced by current intelligence (IQ). Control group and FES neural responses replicated earlier findings in healthy adults. However, a region of anterior medial prefrontal cortex (amPFC) of FES patients showed a different response pattern to that of controls. Unlike healthy controls, patients increased activity in this social cognition region while studying ‘random’ movements of shapes, as compared to the study of movements normally interpreted as ‘intentional’. Conclusions: Mentalizing deficits in FES consists of hypo- and hyper-mentalizing. The neural pattern of FES patients is consistent with deficits in the ability to switch off mentalizing processes in potentially social contexts, instead increasing them when intentionality is not forthcoming. Overall, results demonstrate complexities of theory of mind deficits in schizophrenia that should be considered when offering social cognitive training programs

Sex Determination and Isotopic Analysis of the Nivåfjord Mesolithic Burials, Zealand, Denmark

Since 1992 the prehistoric Nivåfjord in northeast Zealand, Denmark, has yielded an appreciable number of inhumation burials and cremations dating to the Mesolithic, especially the sites of Nivå 10 and Nivågård. Unfortunately, the micro-region is characterised by poor organic preservation, restricting the successful application of biomolecular techniques to human remains, including large-scale radiocarbon dating programmes as well as both stable isotope and ancient DNA analyses. Here, we apply an alternative technique, an acid etch peptide-based method, to determine the sex of eight individuals from Nivå 10 as well as the Nivågård child. Moreover, we revisit the utility of stable carbon (δ13C), nitrogen (δ15N) and sulfur (δ34S) isotope analysis of human tissues to reconstruct the life histories and diets of 10 individuals from Nivå 10 as well as the Nivågård child. To contextualise further, we sampled 14 Capreolus capreolus and three Sus scrofa from the Nivågård site for stable isotope analysis. We demonstrate that sex can successfully be determined from contexts susceptible to poor organic preservation, and show that the Nivågård child spent a proportion of its life outside a sea spray-influenced environment, and consumed significant quantities of marine protein as demonstrated by its δ13C and δ34S values

Avelines's Hole: An Unexpected Twist in the Tale

Aveline’s Hole is the largest known Early Mesolithic cemetery in Britain, previously thought to have no evidence for subsequent burial activity. Thus, it came as some surprise when the results of a recent ancient human DNA study found that, of four individuals from the site yielding genomic data, two showed high levels of ancestry from Early Neolithic Aegean farmers. Radiocarbon dating confirmed that these two individuals were indeed British Early Neolithic in date, while the other two had the expected ‘Western Hunter-Gatherer’ ancestry genomic signatures, with the two groups separated in time by nearly five millennia. Moreover, the two Neolithic samples were both crania, while the two Mesolithic samples were long bones. Given the absence of Neolithic dates in the previous sizeable dating programme combined with the difficult history of the collection, i.e., the WWII bombing of its Bristol repository, this raised the question of whether the crania might in fact be from another site. As we show in this paper, a very strong case can be made that the crania do in fact originate from Aveline’s Hole. Additional radiocarbon dating (14 in total, including the above mentioned four) suggests that about half the cranial elements from the site fall within the Early Neolithic, though there is still no evidence for the deposition of post-cranial remains at this time, nor is there any burial evidence in the long intervening period between the Early Mesolithic and the Early Neolithic. Intriguingly, craniometric analyses of legacy data including three crania lost in the bombing suggest that one, Aveline’s Hole ‘A’, may be Upper Palaeolithicin date. As part of this re-investigation of the human remains from the site, we present new stable carbon and nitrogen isotope analyses that differ significantly from those originally reported for the Early Mesolithic, with the new results more in keeping with other isotopic data for this period. We also present new stable carbon and nitrogen isotope results on human remains from the nearby Early Mesolithic sites of Badger Hole and Greylake, and report new Early Mesolithic radiocarbon dates and isotopic data from Cannington Park Quarry. Clear isotopic differences between the Early Mesolithic and the Neolithic remains can be seen, but these are argued to relate primarily to shifts in the underlying ecological baselines, rather than to differences in types of foods consumed (with the caveat that terrestrial wild and domesticated foods will be isotopically similar). The genetic data are summarised, giving evidence not only of the ancestry of Mesolithic and Neolithic individuals from Aveline’s Hole, but also suggesting something of their physical appearance. The degree of population replacement now indicated by ancient DNA suggests that there was a substantial migration of farmers into Britain at the start of the Neolithic. This new information demonstrates the archaeological importance of Aveline's Hole for both the Mesolithic and Neolithic periods."Funding for nine of the new radiocarbon dates from Aveline’s Hole reported here was provided by NERC’s NRCF programme (NF/2016/2/16). The ancient DNA study was funded by the Wellcome Trust (100713/Z/12/Z), as were three new radiocarbon dates from Aveline’s Hole. The isotopic analysis of the Badger Hole human remains was funded as part of a NERC studentship (NE/K500987/1)."https://www.ubss.org.uk/resources/proceedings/vol28/UBSS_Proc_28_1_9-63.pd

Exchange Bias in Fe@Cr Core–Shell Nanoparticles

We have used X-ray magnetic circular dichroism and magnetometry to study isolated Fe@Cr core−shell nanoparticles with an Fe core diameter of 2.7 nm (850 atoms) and a Cr shell thickness varying between 1 and 2 monolayers. The addition of Cr shells significantly reduces the spin moment but does not change the orbital moment. At least two Cr atomic layers are required to stabilize a ferromagnetic/antiferromagnetic interface and generate the associated exchange bias and increase in coercivity

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit