A neural circuit model of decision uncertainty and change-of-mind

Decision-making is often accompanied by a degree of confidence on whether a choice is correct. Decision uncertainty, or lack in confidence, may lead to change-of-mind. Studies have identified the behavioural characteristics associated with decision confidence or change-of-mind, and their neural correlates. Although several theoretical accounts have been proposed, there is no neural model that can compute decision uncertainty and explain its effects on change-of-mind. We propose a neuronal circuit model that computes decision uncertainty while accounting for a variety of behavioural and neural data of decision confidence and change-of-mind, including testable model predictions. Our theoretical analysis suggests that change-of-mind occurs due to the presence of a transient uncertainty-induced choice-neutral stable steady state and noisy fluctuation within the neuronal network. Our distributed network model indicates that the neural basis of change-of-mind is more distinctively identified in motor-based neurons. Overall, our model provides a framework that unifies decision confidence and change-of-mind

The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.</p> <p>Methods</p> <p>The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose.</p> <p>The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.</p> <p>Trial registration</p> <p>Current Controlled Trials: ISRCTN76912190 and Clinicaltrials.gov ID: NCT00872469</p

Auditory information enhances post-sensory visual evidence during rapid multisensory decision-making

Despite recent progress in understanding multisensory decision-making, a conclusive mechanistic account of how the brain translates the relevant evidence into a decision is lacking. Specifically, it remains unclear whether perceptual improvements during rapid multisensory decisions are best explained by sensory (i.e., ‘Early’) processing benefits or post-sensory (i.e., ‘Late’) changes in decision dynamics. Here, we employ a well-established visual object categorisation task in which early sensory and post-sensory decision evidence can be dissociated using multivariate pattern analysis of the electroencephalogram (EEG). We capitalize on these distinct neural components to identify when and how complementary auditory information influences the encoding of decision-relevant visual evidence in a multisensory context. We show that it is primarily the post-sensory, rather than the early sensory, EEG component amplitudes that are being amplified during rapid audiovisual decision-making. Using a neurally informed drift diffusion model we demonstrate that a multisensory behavioral improvement in accuracy arises from an enhanced quality of the relevant decision evidence, as captured by the post-sensory EEG component, consistent with the emergence of multisensory evidence in higher-order brain areas

AKAPs integrate genetic findings for autism spectrum disorders

Contains fulltext : 115371.pdf (publisher's version ) (Open Access)Autism spectrum disorders (ASDs) are highly heritable, and six genome-wide association studies (GWASs) of ASDs have been published to date. In this study, we have integrated the findings from these GWASs with other genetic data to identify enriched genetic networks that are associated with ASDs. We conducted bioinformatics and systematic literature analyses of 200 top-ranked ASD candidate genes from five published GWASs. The sixth GWAS was used for replication and validation of our findings. Further corroborating evidence was obtained through rare genetic variant studies, that is, exome sequencing and copy number variation (CNV) studies, and/or other genetic evidence, including candidate gene association, microRNA and gene expression, gene function and genetic animal studies. We found three signaling networks regulating steroidogenesis, neurite outgrowth and (glutamatergic) synaptic function to be enriched in the data. Most genes from the five GWASs were also implicated-independent of gene size-in ASDs by at least one other line of genomic evidence. Importantly, A-kinase anchor proteins (AKAPs) functionally integrate signaling cascades within and between these networks. The three identified protein networks provide an important contribution to increasing our understanding of the molecular basis of ASDs. In addition, our results point towards the AKAPs as promising targets for developing novel ASD treatments