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      Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants

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          Abstract

          Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

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          Most cited references54

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

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            Situating the default-mode network along a principal gradient of macroscale cortical organization.

            Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface-and are precisely equidistant-from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.
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              A positive-negative mode of population covariation links brain connectivity, demographics and behavior

              We investigated the relationship between individual subjects’ functional connectomes and 280 behavioral and demographic measures, in a single holistic multivariate analysis relating imaging to non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation; subjects were predominantly spread along a single “positive-negative” axis, linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.
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                Author and article information

                Journal
                Cereb Cortex
                Cereb. Cortex
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                August 2018
                16 May 2018
                16 May 2018
                : 28
                : 8
                : 2959-2975
                Affiliations
                [1 ]Department of Psychology, The University of Edinburgh, Edinburgh, UK
                [2 ]Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
                [3 ]Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
                [4 ]Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Nicosia, Cyprus
                [5 ]Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK
                [6 ]Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
                [7 ]Department of Psychiatry, Queen Margaret Hospital, Dunfermline, UK
                [8 ]NHS Lothian, Edinburgh, UK
                [9 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
                [10 ]Brain Research Imaging Centre, The University of Edinburgh, Edinburgh, UK
                [11 ]Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
                Author notes
                Address correspondence to Stuart J. Ritchie, Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ UK. Email: stuart.ritchie@ 123456ed.ac.uk
                Author information
                http://orcid.org/0000-0002-0538-4774
                Article
                bhy109
                10.1093/cercor/bhy109
                6041980
                29771288
                ceb63a03-d886-42ef-9c05-665ef4c55083
                © The Author(s) 2018. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 January 2018
                : 17 April 2018
                : 20 April 2018
                Page count
                Pages: 17
                Funding
                Funded by: CCACE
                Award ID: MR/K026992/1
                Funded by: MRC
                Award ID: MR/M013111/1
                Funded by: Dementias Platform UK
                Award ID: MR/L015382/1
                Funded by: STRADL
                Award ID: 104036/Z/14/Z
                Categories
                Original Articles

                Neurology
                brain volume,cortical thickness,fmri,sex differences,surface area
                Neurology
                brain volume, cortical thickness, fmri, sex differences, surface area

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