Mediation analysis is routinely adopted by researchers from a wide range of applied disciplines as a statistical tool to disentangle the causal pathways by which an exposure or treatment affects an outcome. The counterfactual framework provides a language for clearly defining path-specific effects of interest and has fostered a principled extension of mediation analysis beyond the context of linear models. This paper describes medflex, an R package that implements some recent developments in mediation analysis embedded within the counterfactual framework. The medflex package offers a set of ready-made functions for fitting natural effect models, a novel class of causal models which directly parameterize the path-specific effects of interest, thereby adding flexibility to existing software packages for mediation analysis, in particular with respect to hypothesis testing and parsimony. In this paper, we give a comprehensive overview of the functionalities of the medflex package.

The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003).

Infrequent count data in psychological research are commonly modelled using zero-inflated Poisson regression. This model can be viewed as a latent mixture of an "always-zero" component and a Poisson component. Hurdle models are an alternative class of two-component models that are seldom used in psychological research, but clearly separate the zero counts and the non-zero counts by using a left-truncated count model for the latter. In this tutorial we revisit both classes of models, and discuss model comparisons and the interpretation of their parameters. As illustrated with an example from relational psychology, both types of models can easily be fitted using the R-package pscl.

The importance of integrating research findings is incontrovertible and procedures for coordinate-based meta-analysis (CBMA) such as Activation Likelihood Estimation (ALE) have become a popular approach to combine results of fMRI studies when only peaks of activation are reported. As meta-analytical findings help building cumulative knowledge and guide future research, not only the quality of such analyses but also the way conclusions are drawn is extremely important. Like classical meta-analyses, coordinate-based meta-analyses can be subject to different forms of publication bias which may impact results and invalidate findings. The file drawer problem refers to the problem where studies fail to get published because they do not obtain anticipated results (e.g. due to lack of statistical significance). To enable assessing the stability of meta-analytical results and determine their robustness against the potential presence of the file drawer problem, we present an algorithm to determine the number of noise studies that can be added to an existing ALE fMRI meta-analysis before spatial convergence of reported activation peaks over studies in specific regions is no longer statistically significant. While methods to gain insight into the validity and limitations of results exist for other coordinate-based meta-analysis toolboxes, such as Galbraith plots for Multilevel Kernel Density Analysis (MKDA) and funnel plots and egger tests for seed-based d mapping, this procedure is the first to assess robustness against potential publication bias for the ALE algorithm. The method assists in interpreting meta-analytical results with the appropriate caution by looking how stable results remain in the presence of unreported information that may differ systematically from the information that is included. At the same time, the procedure provides further insight into the number of studies that drive the meta-analytical results. We illustrate the procedure through an example and test the effect of several parameters through extensive simulations. Code to generate noise studies is made freely available which enables users to easily use the algorithm when interpreting their results.

Studies that validate statistical methods for functional magnetic resonance imaging (fMRI) data often use simulated data to ensure that the ground truth is known. However, simulated fMRI data are almost always generated using in-house procedures because a well-accepted simulation method is lacking. In this article we describe the R package neuRosim, which is a collection of data generation functions for neuroimaging data. We will demonstrate the possibilities to generate data from simple time series to complete 4D images and the possibilities for the user to create her own data generation method.

Recent simulation studies have pointed to the higher power of the test for the mediated effect vs. the test for the total effect, even in the presence of a direct effect. This has motivated applied researchers to investigate mediation in settings where there is no evidence of a total effect. In this paper we provide analytical insight into the circumstances under which higher power of the test for the mediated effect vs. the test for the total effect can be expected in the absence of a direct effect. We argue that the acclaimed power gain is somewhat deceptive and comes with a big price. On the basis of the results, we recommend that when the primary interest lies in mediation only, a significant test for the total effect should not be used as a prerequisite for the test for the indirect effect. However, because the test for the indirect effect is vulnerable to bias when common causes of mediator and outcome are not measured or not accounted for, it should be evaluated in a sensitivity analysis.

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Highlights• The manuscript presents a method to calculate sample sizes for fMRI experiments • The power analysis is based on the estimation of the mixture distribution of null and active peaks • The methodology is validated with simulated and real data. AbstractMounting evidence over the last few years suggest that published neuroscience research suffer from low power, and especially for published fMRI experiments. Not only does low power decrease the chance of detecting a true effect, it also reduces the chance that a statistically significant result indicates a true effect (Ioannidis, 2005). Put another way, findings with the least power will be the least reproducible, and thus a (prospective) power analysis is a critical component of any paper. In this work we present a simple way to characterize the spatial signal in a fMRI study with just two parameters, and a direct way to estimate these two parameters based on an existing study. Specifically, using just (1) the proportion of the brain activated and (2) the average effect size in activated brain regions, we can produce closed form power calculations for given sample size, brain volume and smoothness. This procedure allows one to minimize the cost of an fMRI experiment, while preserving a predefined statistical power. The method is evaluated and illustrated using simulations and real neuroimaging data from the Human Connectome Project. The procedures presented in this paper are made publicly available in an online web-based toolbox available at www.neuropowertools.org.