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      Multiple testing correction over contrasts for brain imaging

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          Abstract

          The multiple testing problem arises not only when there are many voxels or vertices in an image representation of the brain, but also when multiple contrasts of parameter estimates (that represent hypotheses) are tested in the same general linear model. We argue that a correction for this multiplicity must be performed to avoid excess of false positives. Various methods for correction have been proposed in the literature, but few have been applied to brain imaging. Here we discuss and compare different methods to make such correction in different scenarios, showing that one classical and well known method is invalid, and argue that permutation is the best option to perform such correction due to its exactness and flexibility to handle a variety of common imaging situations.

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          Most cited references56

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          Cortical surface-based analysis. I. Segmentation and surface reconstruction.

          Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging. Copyright 1999 Academic Press.
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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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              Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain.

              We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.
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                Author and article information

                Journal
                9215515
                20498
                Neuroimage
                Neuroimage
                NeuroImage
                1053-8119
                1095-9572
                26 May 2021
                19 March 2020
                01 August 2020
                10 June 2021
                : 216
                : 116760
                Affiliations
                [a ]Graduate Program in Electrical and Computer Engineering, Universidade Tecnológica Federal Do Paraná, Curitiba, PR, Brazil
                [b ]Li-Ka Shing Big Data Institute, University of Oxford, UK
                [c ]National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, USA
                Author notes

                CRediT authorship contribution statement

                Bianca A.V. Alberton: Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing - original draft, Writing -review & editing, Visualization. Thomas E. Nichols: Writing - original draft, Conceptualization, Validation. Humberto R. Gamba: Resources, Funding acquisition, Project administration. Anderson M. Winkler: Conceptualization, Methodology, Software, Validation, Formal analysis, Resources, Writing - original draft, Writing - review & editing, Supervision.

                [* ]Corresponding author. biancaalberton@ 123456alunos.utfpr.edu.br (B.A.V. Alberton)
                Article
                NIHMS1706353
                10.1016/j.neuroimage.2020.116760
                8191638
                32201328
                b570742a-51fe-490a-ab96-a92115ede999

                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
                multiple comparisons,multiple testing,brain imaging,permutation tests,contrast correction

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