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      Sex classification using long‐range temporal dependence of resting‐state functional MRI time series

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          Abstract

          A thorough understanding of sex differences that exist in the brains of healthy individuals is crucial for the study of neurological illnesses that exhibit phenotypic differences between males and females. Here we evaluate sex differences in regional temporal dependence of resting‐state brain activity in 195 adult male–female pairs strictly matched for total grey matter volume from the Human Connectome Project. We find that males have more persistent temporal dependence in regions within temporal, parietal, and occipital cortices. Machine learning algorithms trained on regional temporal dependence measures achieve sex classification accuracies up to 81%. Regions with the strongest feature importance in the sex classification task included cerebellum, amygdala, and frontal and occipital cortices. Secondarily, we show that even after strict matching of total gray matter volume, significant volumetric sex differences persist; males have larger absolute cerebella, hippocampi, parahippocampi, thalami, caudates, and amygdalae while females have larger absolute cingulates, precunei, and frontal and parietal cortices. Sex classification based on regional volume achieves accuracies up to 85%, highlighting the importance of strict volume‐matching when studying brain‐based sex differences. Differential patterns in regional temporal dependence between the sexes identifies a potential neurobiological substrate or environmental effect underlying sex differences in functional brain activation patterns.

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          Most cited references39

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex.

            Highly accurate surface models of the cerebral cortex are becoming increasingly important as tools in the investigation of the functional organization of the human brain. The construction of such models is difficult using current neuroimaging technology due to the high degree of cortical folding. Even single voxel misclassifications can result in erroneous connections being created between adjacent banks of a sulcus, resulting in a topologically inaccurate model. These topological defects cause the cortical model to no longer be homeomorphic to a sheet, preventing the accurate inflation, flattening, or spherical morphing of the reconstructed cortex. Surface deformation techniques can guarantee the topological correctness of a model, but are time-consuming and may result in geometrically inaccurate models. In order to address this need we have developed a technique for taking a model of the cortex, detecting and fixing the topological defects while leaving that majority of the model intact, resulting in a surface that is both geometrically accurate and topologically correct.
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              A whole brain fMRI atlas generated via spatially constrained spectral clustering.

              Connectivity analyses and computational modeling of human brain function from fMRI data frequently require the specification of regions of interests (ROIs). Several analyses have relied on atlases derived from anatomical or cyto-architectonic boundaries to specify these ROIs, yet the suitability of atlases for resting state functional connectivity (FC) studies has yet to be established. This article introduces a data-driven method for generating an ROI atlas by parcellating whole brain resting-state fMRI data into spatially coherent regions of homogeneous FC. Several clustering statistics are used to compare methodological trade-offs as well as determine an adequate number of clusters. Additionally, we evaluate the suitability of the parcellation atlas against four ROI atlases (Talairach and Tournoux, Harvard-Oxford, Eickoff-Zilles, and Automatic Anatomical Labeling) and a random parcellation approach. The evaluated anatomical atlases exhibit poor ROI homogeneity and do not accurately reproduce FC patterns present at the voxel scale. In general, the proposed functional and random parcellations perform equivalently for most of the metrics evaluated. ROI size and hence the number of ROIs in a parcellation had the greatest impact on their suitability for FC analysis. With 200 or fewer ROIs, the resulting parcellations consist of ROIs with anatomic homology, and thus offer increased interpretability. Parcellation results containing higher numbers of ROIs (600 or 1,000) most accurately represent FC patterns present at the voxel scale and are preferable when interpretability can be sacrificed for accuracy. The resulting atlases and clustering software have been made publicly available at: http://www.nitrc.org/projects/cluster_roi/. Copyright © 2011 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                eld2024@med.cornell.edu
                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                10.1002/(ISSN)1097-0193
                HBM
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                1065-9471
                1097-0193
                06 July 2020
                September 2020
                : 41
                : 13 ( doiID: 10.1002/hbm.v41.13 )
                : 3567-3579
                Affiliations
                [ 1 ] Department of Radiology Weill Cornell Medicine New York New York USA
                [ 2 ] Brain and Mind Research Institute Weill Cornell Medicine New York New York USA
                [ 3 ] School of Electrical and Computer Engineering Cornell University Ithaca New York USA
                [ 4 ] Meinig School of Biomedical Engineering Cornell University Ithaca New York USA
                Author notes
                [*] [* ] Correspondence

                Elvisha Dhamala, 526 Campus Road, Biotechnology Building, Room 101D, Cornell University, Ithaca, NY, 14850.

                Email: eld2024@ 123456med.cornell.edu

                Author information
                https://orcid.org/0000-0002-8253-6962
                https://orcid.org/0000-0002-5050-8342
                Article
                HBM25030
                10.1002/hbm.25030
                7416025
                32627300
                79886111-e397-4d09-8d4e-8a215a9e2d27
                © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 03 April 2020
                : 27 April 2020
                Page count
                Figures: 4, Tables: 1, Pages: 13, Words: 10431
                Funding
                Funded by: NIH , open-funder-registry 10.13039/100000002;
                Award ID: R01 NS102646‐01A1 (AK), R21 NS104634‐01 (AK), 1R21AG050122 (MRS), R01LM012719 (MRS), R01AG053949 (MRS)
                Funded by: NSF CAREER
                Award ID: 1748377 (MRS)
                Funded by: NSF NeuroNex
                Award ID: 1707312 (MRS)
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                September 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:10.08.2020

                Neurology
                classification,functional mri,machine learning,neuroimaging,sex differences,temporal dependence

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