Cluster Failure Revisited: Impact of First Level Design and Data Quality on Cluster False Positive Rates

Methodological research rarely generates a broad interest, yet our work on the validity of cluster inference methods for functional magnetic resonance imaging (fMRI) created intense discussion on both the minutia of our approach and its implications for the discipline. In the present work, we take on various critiques of our work and further explore the limitations of our original work. We address issues about the particular event-related designs we used, considering multiple event types and randomisation of events between subjects. We consider the lack of validity found with one-sample permutation (sign flipping) tests, investigating a number of approaches to improve the false positive control of this widely used procedure. We found that the combination of a two-sided test and cleaning the data using ICA FIX resulted in nominal false positive rates for all datasets, meaning that data cleaning is not only important for resting state fMRI, but also for task fMRI. Finally, we discuss the implications of our work on the fMRI literature as a whole, estimating that at least 10% of the fMRI studies have used the most problematic cluster inference method (P = 0.01 cluster defining threshold), and how individual studies can be interpreted in light of our findings. These additional results underscore our original conclusions, on the importance of data sharing and thorough evaluation of statistical methods on realistic null data

Hypothesis Testing For Network Data in Functional Neuroimaging

In recent years, it has become common practice in neuroscience to use networks to summarize relational information in a set of measurements, typically assumed to be reflective of either functional or structural relationships between regions of interest in the brain. One of the most basic tasks of interest in the analysis of such data is the testing of hypotheses, in answer to questions such as "Is there a difference between the networks of these two groups of subjects?" In the classical setting, where the unit of interest is a scalar or a vector, such questions are answered through the use of familiar two-sample testing strategies. Networks, however, are not Euclidean objects, and hence classical methods do not directly apply. We address this challenge by drawing on concepts and techniques from geometry, and high-dimensional statistical inference. Our work is based on a precise geometric characterization of the space of graph Laplacian matrices and a nonparametric notion of averaging due to Fr\'echet. We motivate and illustrate our resulting methodologies for testing in the context of networks derived from functional neuroimaging data on human subjects from the 1000 Functional Connectomes Project. In particular, we show that this global test is more statistical powerful, than a mass-univariate approach. In addition, we have also provided a method for visualizing the individual contribution of each edge to the overall test statistic.Comment: 34 pages. 5 figure

Modeling Dynamic Functional Connectivity with Latent Factor Gaussian Processes

Dynamic functional connectivity, as measured by the time-varying covariance of neurological signals, is believed to play an important role in many aspects of cognition. While many methods have been proposed, reliably establishing the presence and characteristics of brain connectivity is challenging due to the high dimensionality and noisiness of neuroimaging data. We present a latent factor Gaussian process model which addresses these challenges by learning a parsimonious representation of connectivity dynamics. The proposed model naturally allows for inference and visualization of time-varying connectivity. As an illustration of the scientific utility of the model, application to a data set of rat local field potential activity recorded during a complex non-spatial memory task provides evidence of stimuli differentiation

Machine Learning for Neuroimaging with Scikit-Learn

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g. multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g. resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain.Comment: Frontiers in neuroscience, Frontiers Research Foundation, 2013, pp.1

Experimental Design Modulates Variance in BOLD Activation: The Variance Design General Linear Model

Typical fMRI studies have focused on either the mean trend in the blood-oxygen-level-dependent (BOLD) time course or functional connectivity (FC). However, other statistics of the neuroimaging data may contain important information. Despite studies showing links between the variance in the BOLD time series (BV) and age and cognitive performance, a formal framework for testing these effects has not yet been developed. We introduce the Variance Design General Linear Model (VDGLM), a novel framework that facilitates the detection of variance effects. We designed the framework for general use in any fMRI study by modeling both mean and variance in BOLD activation as a function of experimental design. The flexibility of this approach allows the VDGLM to i) simultaneously make inferences about a mean or variance effect while controlling for the other and ii) test for variance effects that could be associated with multiple conditions and/or noise regressors. We demonstrate the use of the VDGLM in a working memory application and show that engagement in a working memory task is associated with whole-brain decreases in BOLD variance.Comment: 18 pages, 7 figure

Statistical Network Analysis for Functional MRI: Summary Networks and Group Comparisons

Comparing weighted networks in neuroscience is hard, because the topological properties of a given network are necessarily dependent on the number of edges of that network. This problem arises in the analysis of both weighted and unweighted networks. The term density is often used in this context, in order to refer to the mean edge weight of a weighted network, or to the number of edges in an unweighted one. Comparing families of networks is therefore statistically difficult because differences in topology are necessarily associated with differences in density. In this review paper, we consider this problem from two different perspectives, which include (i) the construction of summary networks, such as how to compute and visualize the mean network from a sample of network-valued data points; and (ii) how to test for topological differences, when two families of networks also exhibit significant differences in density. In the first instance, we show that the issue of summarizing a family of networks can be conducted by adopting a mass-univariate approach, which produces a statistical parametric network (SPN). In the second part of this review, we then highlight the inherent problems associated with the comparison of topological functions of families of networks that differ in density. In particular, we show that a wide range of topological summaries, such as global efficiency and network modularity are highly sensitive to differences in density. Moreover, these problems are not restricted to unweighted metrics, as we demonstrate that the same issues remain present when considering the weighted versions of these metrics. We conclude by encouraging caution, when reporting such statistical comparisons, and by emphasizing the importance of constructing summary networks.Comment: 16 pages, 5 figure