Search

Most people believe in free will. Whether this belief is warranted or not, free will beliefs (FWB) are foundational for many legal systems and reducing FWB has effects on behavior from the motor to the social level. This raises the important question as to which specific FWB people hold. There are many different ways to conceptualize free will, and some might see physical determinism as a threat that might reduce FWB, while others might not. Here, we investigate lay FWB in a large, representative, replicated online survey study in the US and Singapore (n = 1800), assessing differences in FWB with unprecedented depth within and between cultures. Specifically, we assess the relation of FWB, as measured using the Free Will Inventory, to determinism, dualism and related concepts like libertarianism and compatibilism. We find that libertarian, compatibilist, and dualist, intuitions were related to FWB, but that these intuitions were often logically inconsistent. Importantly, direct comparisons suggest that dualism was more predictive of FWB than other intuitions. Thus, believing in free will goes hand-in-hand with a belief in a non-physical mind. Highlighting the importance of dualism for FWB impacts academic debates on free will, which currently largely focus on its relation to determinism. Our findings also shed light on how recent (neuro)scientific findings might impact FWB. Demonstrating physical determinism in the brain need not have a strong impact on FWB, due to a wide-spread belief in dualism., Competing Interests: The authors have declared that no competing interests exist.

Functional neuroimaging has provided evidence for altered function of mesolimbic circuits implicated in reward processing, first and foremost the ventral striatum, in patients with schizophrenia. While such findings based on significant group differences in brain activations can provide important insights into the pathomechanisms of mental disorders, the use of neuroimaging results from standard univariate statistical analysis for individual diagnosis has proven difficult. In this proof of concept study, we tested whether the predictive accuracy for the diagnostic classification of schizophrenia patients vs. healthy controls could be improved using multivariate pattern analysis (MVPA) of regional functional magnetic resonance imaging (fMRI) activation patterns for the anticipation of monetary reward. With a searchlight MVPA approach using support vector machine classification, we found that the diagnostic category could be predicted from local activation patterns in frontal, temporal, occipital and midbrain regions, with a maximal cluster peak classification accuracy of 93% for the right pallidum. Region-of-interest based MVPA for the ventral striatum achieved a maximal cluster peak accuracy of 88%, whereas the classification accuracy on the basis of standard univariate analysis reached only 75%. Moreover, using support vector regression we could additionally predict the severity of negative symptoms from ventral striatal activation patterns. These results show that MVPA can be used to substantially increase the accuracy of diagnostic classification on the basis of task-related fMRI signal patterns in a regionally specific way.

Sustained, long-term cognitive workload is associated with variations and decrements in performance. Such fluctuations in vigilance can be a risk factor especially during dangerous attention demanding activities. Functional MRI studies have shown that attentional performance is correlated with BOLD-signals, especially in parietal and prefrontal cortical regions. An interesting question is whether these BOLD-signals could be measured in real-world scenarios, say to warn in a dangerous workplace whenever a subjects' vigilance is low. Because fMRI lacks the mobility needed for such applications, we tested whether the monitoring of vigilance might be possible using Near-Infrared Spectroscopy (NIRS). NIRS is a highly mobile technique that measures hemodynamics in the surface of the brain. We demonstrate that non-invasive NIRS signals correlate with vigilance. These signals carry enough information to decode subjects' reaction times at a single trial level.

Background: The malaria parasite Plasmodium falciparum EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains., Methods and Findings: Five mAbs specific for F1 or F2 were generated. Three mAbs specific for F2 potently blocked binding of EBA-175 to erythrocytes, and merozoite invasion of erythrocytes (IC(50) 10 to 100 µg/ml IgG in growth inhibition assays). A mAb specific for F1 blocked EBA-175 binding and merozoite invasion less effectively. The difference observed between the IC(50) of F1 and F2 mAbs was not due to differing association and disassociation rates as determined by surface plasmon resonance. Four of the mAbs recognized conformation-dependent epitopes within F1 or F2. Used in combination, F1 and F2 mAbs blocked the binding of native EBA-175 to erythrocytes and inhibited parasite invasion synergistically in vitro. MAb R217, the most potent, did not recognize sporozoites, 3-day hepatocyte stage parasites, nor rings, trophozoites, gametocytes, retorts, ookinetes, and oocysts but recognized 6-day hepatocyte stage parasites, and schizonts. Even though efficient at blocking binding to erythrocytes and inhibiting invasion into erythrocytes, MAb R217 did not inhibit sporozoite invasion and development in hepatocytes in vitro., Conclusions: The role of the F1 and F2 domains in erythrocyte invasion and binding was elucidated with mAbs. These mAbs interfere with native EBA-175 binding to erythrocyte in a synergistic fashion. The stage specific expression of EBA-175 showed that the primary focus of activity was the merozoite stage. A recombinant RII protein vaccine consisting of both F1 and F2 domains that could induce synergistic activity should be optimal for induction of antibody responses that interfere with merozoite invasion of erythrocytes.

Recently, we demonstrated using functional magnetic resonance imaging (fMRI) that the outcome of free decisions can be decoded from brain activity several seconds before reaching conscious awareness. Activity patterns in anterior frontopolar cortex (BA 10) were temporally the first to carry intention-related information and thus a candidate region for the unconscious generation of free decisions. In the present study, the original paradigm was replicated and multivariate pattern classification was applied to functional images of frontopolar cortex, acquired using ultra-high field fMRI at 7 Tesla. Here, we show that predictive activity patterns recorded before a decision was made became increasingly stable with increasing temporal proximity to the time point of the conscious decision. Furthermore, detailed questionnaires exploring subjects' thoughts before and during the decision confirmed that decisions were made spontaneously and subjects were unaware of the evolution of their decision outcomes. These results give further evidence that FPC stands at the top of the prefrontal executive hierarchy in the unconscious generation of free decisions.

Objective: Here, we use pattern-classification to investigate diagnostic information for multiple sclerosis (MS; relapsing-remitting type) in lesioned areas, areas of normal-appearing grey matter (NAGM), and normal-appearing white matter (NAWM) as measured by standard MR techniques., Methods: A lesion mapping was carried out by an experienced neurologist for Turbo Inversion Recovery Magnitude (TIRM) images of individual subjects. Combining this mapping with templates from a neuroanatomic atlas, the TIRM images were segmented into three areas of homogenous tissue types (Lesions, NAGM, and NAWM) after spatial standardization. For each area, a linear Support Vector Machine algorithm was used in multiple local classification analyses to determine the diagnostic accuracy in separating MS patients from healthy controls based on voxel tissue intensity patterns extracted from small spherical subregions of these larger areas. To control for covariates, we also excluded group-specific biases in deformation fields as a potential source of information., Results: Among regions containing lesions a posterior parietal WM area was maximally informative about the clinical status (96% accuracy, p<10(-13)). Cerebellar regions were maximally informative among NAGM areas (84% accuracy, p<10(-7)). A posterior brain region was maximally informative among NAWM areas (91% accuracy, p<10(-10))., Interpretation: We identified regions indicating MS in lesioned, but also NAGM, and NAWM areas. This complements the current perception that standard MR techniques mainly capture macroscopic tissue variations due to focal lesion processes. Compared to current diagnostic guidelines for MS that define areas of diagnostic information with moderate spatial specificity, we identified hotspots of MS associated tissue alterations with high specificity defined on a millimeter scale.

A Plasmodium falciparum 3D7 strain Apical Membrane Antigen-1 (AMA1) vaccine, formulated with AS02(A) adjuvant, slowed parasite growth in a recent Phase 1/2a trial, however sterile protection was not observed. We tested this AS02(A), and a Montanide ISA720 (ISA) formulation of 3D7 AMA1 in Aotus monkeys. The 3D7 parasite does not invade Aotus erythrocytes, hence two heterologous strains, FCH/4 and FVO, were used for challenge, FCH/4 AMA1 being more homologous to 3D7 than FVO AMA1. Following three vaccinations, the monkeys were challenged with 50,000 FCH/4 or 10,000 FVO parasites. Three of the six animals in the AMA+ISA group were protected against FCH/4 challenge. One monkey did not become parasitemic, another showed only a short period of low level parasitemia that self-cured, and a third animal showed a delay before exhibiting its parasitemic phase. This is the first protection shown in primates with a recombinant P. falciparum AMA1 without formulation in Freund's complete adjuvant. No animals in the AMA+AS02(A) group were protected, but this group exhibited a trend towards reduced growth rate. A second group of monkeys vaccinated with AMA+ISA vaccine was not protected against FVO challenge, suggesting strain-specificity of AMA1-based protection. Protection against FCH/4 strain correlated with the quantity of induced antibodies, as the protected animals were the only ones to have in vitro parasite growth inhibitory activity of >70% at 1:10 serum dilution; immuno-fluorescence titers >8,000; ELISA titers against full-length AMA1 >300,000 and ELISA titer against AMA1 domains1+2 >100,000. A negative correlation between log ELISA titer and day 11 cumulative parasitemia (Spearman rank r = -0.780, p value = 0.0001), further confirmed the relationship between antibody titer and protection. High titers of cross-strain inhibitory antibodies against AMA1 are therefore critical to confer solid protection, and the Aotus model can be used to down-select future AMA1 formulations, prior to advanced human trials.

Background: The perception of brightness depends on spatial context: the same stimulus can appear light or dark depending on what surrounds it. A less well-known but equally important contextual phenomenon is that the colour of a stimulus can also alter its brightness. Specifically, stimuli that are more saturated (i.e. purer in colour) appear brighter than stimuli that are less saturated at the same luminance. Similarly, stimuli that are red or blue appear brighter than equiluminant yellow and green stimuli. This non-linear relationship between stimulus intensity and brightness, called the Helmholtz-Kohlrausch (HK) effect, was first described in the nineteenth century but has never been explained. Here, we take advantage of the relative simplicity of this 'illusion' to explain it and contextual effects more generally, by using a simple Bayesian ideal observer model of the human visual ecology. We also use fMRI brain scans to identify the neural correlates of brightness without changing the spatial context of the stimulus, which has complicated the interpretation of related fMRI studies., Results: Rather than modelling human vision directly, we use a Bayesian ideal observer to model human visual ecology. We show that the HK effect is a result of encoding the non-linear statistical relationship between retinal images and natural scenes that would have been experienced by the human visual system in the past. We further show that the complexity of this relationship is due to the response functions of the cone photoreceptors, which themselves are thought to represent an efficient solution to encoding the statistics of images. Finally, we show that the locus of the response to the relationship between images and scenes lies in the primary visual cortex (V1), if not earlier in the visual system, since the brightness of colours (as opposed to their luminance) accords with activity in V1 as measured with fMRI., Conclusions: The data suggest that perceptions of brightness represent a robust visual response to the likely sources of stimuli, as determined, in this instance, by the known statistical relationship between scenes and their retinal responses. While the responses of the early visual system (receptors in this case) may represent specifically the statistics of images, post receptor responses are more likely represent the statistical relationship between images and scenes. A corollary of this suggestion is that the visual cortex is adapted to relate the retinal image to behaviour given the statistics of its past interactions with the sources of retinal images: the visual cortex is adapted to the signals it receives from the eyes, and not directly to the world beyond.