Bayesian parametric estimation of stop-signal reaction time distributions

The cognitive concept of response inhibition can be measured using the stop-signal paradigm. In this paradigm, participants perform a two-choice response time (RT) task where, on some of the trials, the primary task is interrupted by a stop-signal that prompts participants to withhold their response. The dependent variable of interest is the latency of the unobservable stop response (stop signal reaction time or SSRT). Based on the horse-race model (Logan & Cowan, 1984), several methods have been developed to estimate SSRTs. None of these approaches allow for the accurate estimation of the entire distribution of SSRTs. Here we introduce a Bayesian parametric approach that addresses this limitation. Our method is based on the assumptions of the horse-race model and rests on the concept of censored distributions. We treat response inhibition as a censoring mechanism, where the distribution of RTs on the primary task (go RTs) is censored by the distribution of SSRTs. The method assumes that go RTs and SSRTs are ex-Gaussian distributed and uses Markov chain Monte Carlo sampling to obtain posterior distributions for the model parameters. The method can be applied to individual as well as hierarchical data structures. We present the results of a number of parameter recovery and robustness studies and apply our approach to published data from a stop-signal experiment

Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton

Meckel-Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder caused by mutations in genes that encode components of the primary cilium and basal body. Here we show that two MKS proteins, MKS1 and meckelin, that are required for centrosome migration and ciliogenesis interact with actin-binding isoforms of nesprin-2 (nuclear envelope spectrin repeat protein 2, also known as Syne-2 and NUANCE). Nesprins are important scaffold proteins for maintenance of the actin cytoskeleton, nuclear positioning and nuclear-envelope architecture. However, in ciliated-cell models, meckelin and nesprin-2 isoforms colocalized at filopodia prior to the establishment of cell polarity and ciliogenesis. Loss of nesprin-2 and nesprin-1 shows that both mediate centrosome migration and are then essential for ciliogenesis, but do not otherwise affect apical-basal polarity. Loss of meckelin (by siRNA and in a patient cell-line) caused a dramatic remodelling of the actin cytoskeleton, aberrant localization of nesprin-2 isoforms to actin stress-fibres and activation of RhoA signalling. These findings further highlight the important roles of the nesprins during cellular and developmental processes, particularly in general organelle positioning, and suggest that a mechanistic link between centrosome positioning, cell polarity and the actin cytoskeleton is required for centrosomal migration and is essential for early ciliogenesis