Redressing the emperor in causal clothing

Over-flexibility in the definition of Friston blankets obscures a key distinction between observational and interventional inference. The latter requires cognizers form not just a causal representation of the world but also of their own boundary and relationship with it, in order to diagnose the consequences of their actions. We suggest this locates the blanket in the eye of the beholder

Causal learning from interventions and dynamics in continuous time

Event timing and interventions are important and intertwinedcues to causal structure, yet they have typically been studiedseparately. We bring them together for the first time in an ex-periment where participants learn causal structure by perform-ing interventions in continuous time. We contrast learning inacyclic and cyclic devices, with reliable and unreliable cause–effect delays. We show that successful learners use interven-tions to structure and simplify their interactions with the de-vices and that we can capture judgment patterns with heuristicsbased on online construction and testing of a single structura

Time in causal structure learning

A large body of research has explored how the time between two events affects judgments of causal strength between them. In this article, we extend this work in 4 experiments that explore the role of temporal information in causal structure induction with multiple variables. We distinguish two qualitatively different types of information: The order in which events occur, and the temporal intervals between those events. We focus on one-shot learning in Experiment 1. In Experiment 2, we explore how people integrate evidence from multiple observations of the same causal device. Participants' judgments are well predicted by a Bayesian model that rules out causal structures that are inconsistent with the observed temporal order, and favors structures that imply similar intervals between causally connected components. In Experiments 3 and 4, we look more closely at participants' sensitivity to exact event timings. Participants see three events that always occur in the same order, but the variability and correlation between the timings of the events is either more consistent with a chain or a fork structure. We show, for the first time, that even when order cues do not differentiate, people can still make accurate causal structure judgments on the basis of interval variability alone

Formalizing Neurath's ship:Approximate algorithms for online causal learning

Higher-level cognition depends on the ability to learn models of the world. We can characterize this at the computational level as a structure-learning problem with the goal of best identifying the prevailing causal relationships among a set of relata. However, the computational cost of performing exact Bayesian inference over causal models grows rapidly as the number of relata increases. This implies that the cognitive processes underlying causal learning must be substantially approximate. A powerful class of approximations that focuses on the sequential absorption of successive inputs is captured by the Neurath's ship metaphor in philosophy of science, where theory change is cast as a stochastic and gradual process shaped as much by people's limited willingness to abandon their current theory when considering alternatives as by the ground truth they hope to approach. Inspired by this metaphor and by algorithms for approximating Bayesian inference in machine learning, we propose an algorithmic-level model of causal structure learning under which learners represent only a single global hypothesis that they update locally as they gather evidence. We propose a related scheme for understanding how, under these limitations, learners choose informative interventions that manipulate the causal system to help elucidate its workings. We find support for our approach in the analysis of four experiments

A fluorescent approach for identifying P2X1 ligands.

There are no commercially available, small, receptor-specific P2X1 ligands. There are several synthetic derivatives of the natural agonist ATP and some structurally-complex antagonists including compounds such as PPADS, NTP-ATP, suramin and its derivatives (e.g. NF279, NF449). NF449 is the most potent and selective ligand, but potencies of many others are not particularly high and they can also act at other P2X, P2Y and non-purinergic receptors. While there is clearly scope for further work on P2X1 receptor pharmacology, screening can be difficult owing to rapid receptor desensitisation. To reduce desensitisation substitutions can be made within the N-terminus of the P2X1 receptor, but these could also affect ligand properties. An alternative is the use of fluorescent voltage-sensitive dyes that respond to membrane potential changes resulting from channel opening. Here we utilised this approach in conjunction with fragment-based drug-discovery. Using a single concentration (300 μM) we identified 46 novel leads from a library of 1443 fragments (hit rate = 3.2%). These hits were independently validated by measuring concentration-dependence with the same voltage-sensitive dye, and by visualising the competition of hits with an Alexa-647-ATP fluorophore using confocal microscopy; confocal yielded kon (1.142 × 10(6) M(-1) s(-1)) and koff (0.136 s(-1)) for Alexa-647-ATP (Kd = 119 nM). The identified hit fragments had promising structural diversity. In summary, the measurement of functional responses using voltage-sensitive dyes was flexible and cost-effective because labelled competitors were not needed, effects were independent of a specific binding site, and both agonist and antagonist actions were probed in a single assay. The method is widely applicable and could be applied to all P2X family members, as well as other voltage-gated and ligand-gated ion channels. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'.Our thanks are given to Richard Evans for the P2X1 cDNA, and to Prof. Oliver Mühlemann for kindly providing lab space for M-DR. M-DR was supported by the HOLCIM Stiftung zur Förderung der wissenschaftlichen Fortbildung. The British Heart Foundation supported AJT (grant; PG/13/39/30293) and RWF (grant; RG/09/003/27122).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neuropharm.2015.05.01

Temporal Binding, Causation, and Agency: Developing a New Theoretical Framework

In temporal binding, the temporal interval between one event and another, occurring some time later, is subjectively compressed. We discuss two ways in which temporal binding has been conceptualized. In studies showing temporal binding between a voluntary action and its causal consequences, such binding is typically interpreted as providing a measure of an implicit or pre-reflective “sense of agency.” However, temporal binding has also been observed in contexts not involving voluntary action, but only the passive observation of a cause–effect sequence. In those contexts, it has been interpreted as a top-down effect on perception reflecting a belief in causality. These two views need not be in conflict with one another, if one thinks of them as concerning two separate mechanisms through which temporal binding can occur. In this paper, we explore an alternative possibility: that there is a unitary way of explaining temporal binding both within and outside the context of voluntary action as a top-down effect on perception reflecting a belief in causality. Any such explanation needs to account for ways in which agency, and factors connected with agency, has been shown to affect the strength of temporal binding. We show that principles of causal inference and causal selection already familiar from the literature on causal learning have the potential to explain why the strength of people's causal beliefs can be affected by the extent to which they are themselves actively involved in bringing about events, thus in turn affecting binding

The developmental profile of temporal binding: From childhood to adulthood.

Temporal binding refers to a phenomenon whereby the time interval between a cause and its effect is perceived as shorter than the same interval separating two unrelated events. We examined the developmental profile of this phenomenon by comparing the performance of groups of children (aged 6–7, 7–8, and 9–10 years) and adults on a novel interval estimation task. In Experiment 1, participants made judgements about the time interval between (a) their button press and a rocket launch, and (b) a non-causal predictive signal and rocket launch. In Experiment 2, an additional causal condition was included in which participants made judgements about the interval between an experimenter’s button press and the launch of a rocket. Temporal binding was demonstrated consistently and did not change in magnitude with age: estimates of delay were shorter in causal contexts for both adults and children. In addition, the magnitude of the binding effect was greater when participants themselves were the cause of an outcome compared with when they were mere spectators. This suggests that although causality underlies the binding effect, intentional action may modulate its magnitude. Again, this was true of both adults and children. Taken together, these results are the first to suggest that the binding effect is present and developmentally constant from childhood into adulthood