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How convincing is current evidence for unconscious processing? Recently, a major criticism suggested that this evidence might be fully explained by a mere statistical phenomenon: regression to the mean (RttM). Since excluding participants based on an awareness assessment is a common practice in such studies, this post-hoc data selection might evoke RttM and lead to false effects that are driven by aware participants wrongfully classified as unaware. Here, we examined this criticism using both simulations and data from 15 studies probing unconscious processing (43 effects overall). In line with the original criticism, we confirmed that the reliability of awareness measures in the field is concerningly low. Yet using simulations we showed that reliability measures might be unsuitable for estimating error in awareness measures. Furthermore, we examined three proposed ways to assess whether an effect is genuine or reflects RttM; all suffered from substantial limitations, such as a lack of power or an unjustified linearity assumption. Accordingly, we suggest a new nonparametric solution, which enjoys high sensitivity and relatively high power. Together, this work emphasizes the need to account for the contribution of measurement error to effects of unconscious processing. It further suggests a way to meet the important challenge posed by RttM, in an attempt to establish a reliable and robust corpus of knowledge in studying unconscious processing.

We would like to congratulate Dr. Eric Gibson on his very scholarly review on the p-value and the controversy surrounding its role in the replicability crisis. It was written from a point of view t...

Contemporary symptom-based diagnosis of post-traumatic stress disorder (PTSD) largely overlooks related neurobehavioral mechanisms and relies entirely on subjective interpersonal reporting. Previous studies associating biomarkers with PTSD have mostly used symptom-based diagnosis as the main outcome measure, disregarding the wide variability and richness of PTSD phenotypical features. Here, we aimed to computationally derive potential biomarkers that could efficiently differentiate PTSD subtypes among recent trauma survivors. A three-staged semi-unsupervised method (“3C”) was used to firstly categorize individuals by current PTSD symptom severity, then derive clusters based on clinical features related to PTSD (e.g. anxiety and depression), and finally to classify participants’ cluster membership using objective multi-domain features. A total of 256 features were extracted from psychometrics, cognitive functioning, and both structural and functional MRI data, obtained from 101 adult civilians (age = 34.80 ± 11.95; 51 females) evaluated within 1 month of trauma exposure. The features that best differentiated cluster membership were assessed by importance analysis, classification tree, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural MRI domain), in-task amygdala’s functional connectivity with the insula and thalamus (functional MRI domain), executive function and cognitive flexibility (cognitive testing domain) best differentiated between two clusters associated with PTSD severity. Cross-validation established the results’ robustness and consistency within this sample. The neural and cognitive potential biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral mechanisms associated with PTSD and demonstrate the usefulness of standardized and objective measurements as differentiating clinical sub-classes shortly after trauma.

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice., Optimizing approach-avoidance behavior calls for neural encoding of related motivation outcomes. Here, the authors show that behavioral choice under conflict relies on differential neuronal firing patterns after punishment, in which mPFC neurons decode the outcome’s value and MTL neurons follow by reducing subsequent approach.

BACKGROUND: Low hippocampal volume could serve as an early risk factor for Post-traumatic Stress Disorder (PTSD) in interaction with other brain anomalies of developmental origin. One such anomaly may well be a presence of large Cavum Septum Pellucidum (CSP), which has been loosely associated with PTSD. Here, we performed a longitudinal prospective study of recent trauma survivors. We hypothesized that at one-month after trauma exposure, the relation between hippocampal volume and PTSD symptom severity will be moderated by CSP volume, and that this early interaction will account for persistent PTSD symptoms at subsequent time-points. METHODS: 171 adults (87 females, average age=34.22, range=18–65) admitted to a general hospital’s emergency department following a traumatic event, underwent clinical assessment and structural MRI within one-month after trauma. Follow-up clinical evaluations were conducted at six (n=97) and fourteen (n=78) months after trauma. Hippocampus and CSP volumes were measured automatically by FreeSurfer software and verified manually by a neuroradiologist. RESULTS: At one-month following trauma, CSP volume significantly moderated the relation between hippocampal volume and PTSD severity (p=0.026), and this interaction further predicted symptom severity at fourteen months post-trauma (p=0.018). Specifically, individuals with smaller hippocampus and larger CSP at one-month post-trauma, showed more severe symptoms at one- and fourteen months following trauma exposure. CONCLUSIONS: Our study provides evidence for an early neuroanatomical risk factors for PTSD, which could also predict the progression of the disorder in the year following trauma exposure. Such a simple-to-acquire neuroanatomical signature for PTSD could guide early management, as well as long-term monitoring. TRIAL REGISTRATION: Neurobehavioral Moderators of Post-traumatic Disease Trajectories. ClinicalTrials.gov registration: NCT03756545. https://clinicaltrials.gov/ct2/show/NCT03756545

Identifying disease signatures in order to facilitate accurate diagnosis/treatment has been the focus of research efforts in the last decade. However, the term "disease signature" has not been properly defined, resulting in inconsistencies between studies, as well as limited ability to fully utilize the tools/information available in the evolving field of healthcare big data. Research was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The search (in PubMed, Cochrane, and Web of Science) was limited to English articles published up to 31/12/2016. The search string was "disease signature" OR "disease signatures" OR "disease fingerprint" OR "disease fingerprints" OR "subtype signature" OR "subtype signatures" OR "subgroup signature" OR "subgroup signatures." The full text of the articles was reviewed to determine the meaning of the phrase "disease signature" as well as the context of its use. Of 285 articles identified in the search, 129 were included in the final analysis. The term disease signature was first found in an article from 2001. In the last 10 years, the use of the term increased by approximately ninefold, which is double the general increase in the number of published articles. Only one article attempted to define the term. The two major medical fields where the term was used were oncology (31%) and neurology (20%); 71% of the identified articles used a single biomarker to define the term, 13% of the articles used a pair of biomarkers, and 16% used signatures with multiple biomarker; in 42% of the identified articles, genomic biomarkers were used for the signature, in 17% measurements of biochemical compounds in body fluids, and in 10%, changes in imaging studies were used for the signature. Our findings identified a lack of consistency in defining the term disease signature. We suggest a novel hierarchical multidimensional concept for this term that would combine both current approaches for identifying diseases (one focusing on undesired effects of the disease and the other on its causes). This model can improve disease signature definition consistency which will enable to generalize and classify diseases, resulting in more precise treatments and better outcomes. Ultimately, this model could lead to developing a statistical confidence in a disease signature that would allow physicians/patients to estimate the precision of the diagnosis, which, in turn, may have important implications on patients' prognosis and treatment.

Previous studies have suggested that there are common mechanisms between perceptual and value-based processes. For instance, both perceptual and value-based choices are highly influenced by the context in which the choices are made. However, the mechanisms which allow context to influence our choice process as well as the extent of the similarity between the perceptual and preferential processes are still unclear. In this study, we examine a within-subject relation between the attraction effect, which is a well-known effect of context on preferential choice, and the Gestalt law of proximity. Then, we aim to use this link to better understand the mechanisms underlying the attraction effect. We performed one study followed by an additional pre-registered replication study, where subjects performed a Gestalt-psychophysical task and a decoy task. Comparing the behavioral sensitivity of each subject in both tasks, we found that the more susceptible a subject is to the proximity law, the more she displayed the attraction effect. These results demonstrate a within-subject relation between a perceptual phenomenon (proximity law) and a value-based bias (attraction effect) which further strengthens the notion of common rules between perceptual and value-based processing. Moreover, this suggests that the mechanism underlying the attraction effect is related to grouping by proximity with attention as a mediator.

Contemporary symptom-based diagnosis of Post-traumatic Stress Disorder (PTSD) largely overlooks related neurobehavioral findings and rely entirely on subjective interpersonal reporting. Previous studies associating objective biomarkers with PTSD have mostly used the disorder’s symptom-based diagnosis as main outcome measure, overlooking the actual clustering and richness of phenotypical features associated with PTSD. Here, we aimed to computationally derive potential neurocognitive biomarkers that could efficiently differentiate PTSD subtypes, based on an observational cohort study of recent trauma survivors. A three-staged semi-unsupervised method (“3C”) was used to categorize trauma survivors based on current PTSD diagnostics, derive clusters of PTSD based on features related to symptom load, and to classify participants’ cluster membership using objective features. A total of 256 features were extracted from psychometrics, cognitive, structural and functional neuroimaging data, obtained from 101 adult civilians (age=34.80±11.95, 51 females) evaluated within a month of trauma exposure. Multi-domain features that best differentiated cluster membership were indicated by using importance analysis, classification trees, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural domain), in-task amygdala’s functional connectivity with the insula and thalamus (functional domain), executive function and cognitive flexibility (cognitive domain) best differentiated between two clusters related to PTSD severity. Cross-validation established the results’ robustness and consistency within this sample. Multi-domain biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral PTSD features, supporting the future use of standardized and objective measurements to more precisely identify psychopathology subgroups shortly after trauma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rational choice theory assumes optimality in decision-making. Violations of a basic axiom of economic rationality known as “Independence of Irrelevant Alternatives” (IIA) have been demonstrated in both humans and animals and could stem from common neuronal constraints. Here we develop tests for IIA in the nematode Caenorhabditis elegans, an animal with only 302 neurons, using olfactory chemotaxis assays. We find that in most cases C. elegans make rational decisions. However, by probing multiple neuronal architectures using various choice sets, we show that violations of rationality arise when the circuit of olfactory sensory neurons is asymmetric. We further show that genetic manipulations of the asymmetry between the AWC neurons can make the worm irrational. Last, a context-dependent normalization-based model of value coding and gain control explains how particular neuronal constraints on information coding give rise to irrationality. Thus, we demonstrate that bounded rationality could arise due to basic neuronal constraints., Innate odor preferences in C. elegans are controlled by the activation of a pair of olfactory sensory neurons. Here, the authors show that asymmetric activation of the AWCON and AWCOFF neurons can lead to irrational olfactory preferences that are explained by a model of normalization of sensory gain control.

Rational choice theory assumes optimality in decision-making. Violations of a basic axiom of economic rationality known as “Independence of Irrelevant Alternatives” (IIA), have been demonstrated in both humans and animals, and could stem from common neuronal constraints. We developed tests for IIA in the nematode Caenorhabditis elegans, an animal with only 302 neurons, using olfactory chemotaxis assays. We found that in most cases C. elegans make rational decisions. However, by probing multiple neuronal architectures using various choice sets, we show that asymmetric sensation of odor options by the AWCON neuron can lead to violations of rationality. We further show that genetic manipulations of the asymmetry between the AWC neurons can make the worm rational or irrational. Last, a normalization-based model of value coding and gain control explains how particular neuronal constraints on information coding give rise to irrationality. Thus, we demonstrate that bounded rationality could arise due to basic neuronal constraints.