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      Moderated t-tests for group-level fMRI analysis

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      , , *
      NeuroImage
      Moderated t-test, fMRI, Group analysis, LIMMA, LIMMI

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          Abstract

          In recent years, there has been significant criticism of functional magnetic resonance imaging (fMRI) studies with small sample sizes. The argument is that such studies have low statistical power, as well as reduced likelihood for statistically significant results to be true effects. The prevalence of these studies has led to a situation where a large number of published results are not replicable and likely false. Despite this growing body of evidence, small sample fMRI studies continue to be regularly performed; likely due to the high cost of scanning. In this report we investigate the use of a moderated t-statistic for performing group-level fMRI analysis to help alleviate problems related to small sample sizes. The proposed approach, implemented in the popular R-package LIMMA (linear models for microarray data), has found wide usage in the genomics literature for dealing with similar issues. Utilizing task-based fMRI data from the Human Connectome Project (HCP), we compare the performance of the moderated t-statistic with the standard t-statistic, as well as the pseudo t-statistic commonly used in non-parametric fMRI analysis. We find that the moderated t-test significantly outperforms both alternative approaches for studies with sample sizes less than 40 subjects. Further, we find that the results were consistent both when using voxel-based and cluster-based thresholding. We also introduce an R-package, LIMMI (linear models for medical images), that provides a quick and convenient way to apply the method to fMRI data.

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          Most cited references39

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          limma powers differential expression analyses for RNA-sequencing and microarray studies

          limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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            The minimal preprocessing pipelines for the Human Connectome Project.

            The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinate spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP's acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements to the pipelines. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Power failure: why small sample size undermines the reliability of neuroscience.

              A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.
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                Author and article information

                Journal
                9215515
                20498
                Neuroimage
                Neuroimage
                NeuroImage
                1053-8119
                1095-9572
                13 July 2021
                04 May 2021
                15 August 2021
                15 August 2021
                : 237
                : 118141
                Affiliations
                Department of Biostatistics, Johns Hopkins University, Baltimore, MD, United States
                Author notes

                Credit authorship contribution statement

                Guoqing Wang: Conceptualization, Methodology, Software, Formal analysis, Writing - original draft. John Muschelli: Formal analysis, Software, Writing - review & editing. Martin A. Lindquist: Conceptualization, Methodology, Writing - review & editing, Supervision, Funding acquisition.

                [* ]Corresponding author. mlindqui@ 123456jhsph.edu (M.A. Lindquist).
                Article
                NIHMS1723752
                10.1016/j.neuroimage.2021.118141
                8295929
                33962000
                3adfedb8-1ab7-4ff5-8f06-152d7883fba8

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/)

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                Neurosciences
                moderated t-test,fmri,group analysis,limma,limmi
                Neurosciences
                moderated t-test, fmri, group analysis, limma, limmi

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