Sex Classification by Resting State Brain Connectivity

Abstract A large amount of brain imaging research has focused on group studies delineating differences between males and females with respect to both cognitive performance as well as structural and functional brain organization. To supplement existing findings, the present study employed a machine learning approach to assess how accurately participants’ sex can be classified based on spatially specific resting state (RS) brain connectivity, using 2 samples from the Human Connectome Project (n1 = 434, n2 = 310) and 1 fully independent sample from the 1000BRAINS study (n = 941). The classifier, which was trained on 1 sample and tested on the other 2, was able to reliably classify sex, both within sample and across independent samples, differing both with respect to imaging parameters and sample characteristics. Brain regions displaying highest sex classification accuracies were mainly located along the cingulate cortex, medial and lateral frontal cortex, temporoparietal regions, insula, and precuneus. These areas were stable across samples and match well with previously described sex differences in functional brain organization. While our data show a clear link between sex and regionally specific brain connectivity, they do not support a clear-cut dimorphism in functional brain organization that is driven by sex alone.

[1]  Tim Oates,et al.  Efficient progressive sampling , 1999, KDD '99.

[2]  Kenneth Hugdahl,et al.  Language lateralization and cognitive control across the menstrual cycle assessed with a dichotic-listening paradigm , 2012, Psychoneuroendocrinology.

[3]  Wim Van Hecke,et al.  Stability of resting state networks in the female brain during hormonal changes and their relation to premenstrual symptoms , 2015, Brain Research.

[4]  K. Davis,et al.  Cognitive and default‐mode resting state networks: Do male and female brains “rest” differently? , 2010, Human brain mapping.

[5]  Alan C. Evans,et al.  Growing Together and Growing Apart: Regional and Sex Differences in the Lifespan Developmental Trajectories of Functional Homotopy , 2010, The Journal of Neuroscience.

[6]  Richard A. Lippa,et al.  Joel et al.'s method systematically fails to detect large, consistent sex differences , 2016, Proceedings of the National Academy of Sciences.

[7]  Thomas E. Nichols,et al.  Functional connectomics from resting-state fMRI , 2013, Trends in Cognitive Sciences.

[8]  Yong He,et al.  Hemisphere- and gender-related differences in small-world brain networks: A resting-state functional MRI study , 2011, NeuroImage.

[9]  R W Cox,et al.  Language processing is strongly left lateralized in both sexes. Evidence from functional MRI. , 1999, Brain : a journal of neurology.

[10]  Steen Moeller,et al.  Evaluation of slice accelerations using multiband echo planar imaging at 3T , 2013, NeuroImage.

[11]  S. Baron-Cohen,et al.  Neuroscience and Biobehavioral Reviews a Meta-analysis of Sex Differences in Human Brain Structure , 2022 .

[12]  D. Halpern,et al.  The new science of cognitive sex differences , 2014, Trends in Cognitive Sciences.

[13]  Simon B Eickhoff,et al.  Meta-analysis in human neuroimaging: computational modeling of large-scale databases. , 2014, Annual review of neuroscience.

[14]  Emily J. Ward,et al.  Patterns in the human brain mosaic discriminate males from females , 2016, Proceedings of the National Academy of Sciences.

[15]  Alan C. Evans,et al.  Studying variability in human brain aging in a population-based German cohort—rationale and design of 1000BRAINS , 2014, Front. Aging Neurosci..

[16]  Kate Tchanturia,et al.  Sex differences in theory of mind: A male advantage on Happé's “cartoon” task , 2007 .

[17]  J. J. Pekar,et al.  Sex differences in cerebral laterality of language and visuospatial processing , 2006, Brain and Language.

[18]  Mikkel Wallentin,et al.  Putative sex differences in verbal abilities and language cortex: A critical review , 2009, Brain and Language.

[19]  Anne Fausto-Sterling,et al.  Beyond sex differences: new approaches for thinking about variation in brain structure and function , 2016, Philosophical Transactions of the Royal Society B: Biological Sciences.

[20]  M. D. Giudice,et al.  On the Real Magnitude of Psychological Sex Differences , 2009 .

[21]  Jonathan D. Rosenblatt Multivariate revisit to “sex beyond the genitalia” , 2016, Proceedings of the National Academy of Sciences.

[22]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[23]  Susan D. Voyer,et al.  Sex differences in visual-spatial working memory: A meta-analysis , 2016, Psychonomic Bulletin & Review.

[24]  P. V. Rekkas,et al.  Progesterone mediates brain functional connectivity changes during the menstrual cycle—a pilot resting state MRI study , 2015, Front. Neurosci..

[25]  Ludovica Griffanti,et al.  Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers , 2014, NeuroImage.

[26]  Yu Zhang,et al.  The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture , 2016, Cerebral cortex.

[27]  Lisa A. Kilpatrick,et al.  Oral contraceptive pill use and menstrual cycle phase are associated with altered resting state functional connectivity , 2014, NeuroImage.

[28]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[29]  L. Jäncke Sex/gender differences in cognition, neurophysiology, and neuroanatomy , 2018, F1000Research.

[30]  Evan M. Gordon,et al.  Local-Global Parcellation of the Human Cerebral Cortex From Intrinsic Functional Connectivity MRI , 2017, bioRxiv.

[31]  Susanne Weis,et al.  Sex differences and menstrual cycle effects in cognitive and sensory resting state networks , 2017, Brain and Cognition.

[32]  D. Halpern Sex Differences in Cognitive Abilities , 1986 .

[33]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[34]  Ben Glocker,et al.  Metric learning with spectral graph convolutions on brain connectivity networks , 2018, NeuroImage.

[35]  Eileen Luders,et al.  Decoding gender dimorphism of the human brain using multimodal anatomical and diffusion MRI data , 2013, NeuroImage.

[36]  Danilo Bzdok,et al.  Classical Statistics and Statistical Learning in Imaging Neuroscience , 2016, Front. Neurosci..

[37]  Mark E Bastin,et al.  Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants , 2017, bioRxiv.

[38]  Mark W. Woolrich,et al.  Resting-state fMRI in the Human Connectome Project , 2013, NeuroImage.

[39]  Alan C. Evans,et al.  Enhancement of MR Images Using Registration for Signal Averaging , 1998, Journal of Computer Assisted Tomography.

[40]  Simon B. Eickhoff,et al.  An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data , 2013, NeuroImage.

[41]  J. Hyde,et al.  Magnitude of psychological gender differences. Another side to the story. , 1995, The American psychologist.

[42]  Bertrand Thirion,et al.  Inter-subject Registration of Functional Images: Do We Need Anatomical Images? , 2018, Front. Neurosci..

[43]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

[44]  Chao Zhang,et al.  Functional connectivity predicts gender: Evidence for gender differences in resting brain connectivity , 2018, Human brain mapping.

[45]  Mary Beth Nebel,et al.  The impact of T1 versus EPI spatial normalization templates for fMRI data analyses , 2017, Human brain mapping.

[46]  Karl J. Friston,et al.  Structural and Functional Brain Networks: From Connections to Cognition , 2013, Science.

[47]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[48]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[49]  Daniel S. Margulies,et al.  Sex beyond the genitalia: The human brain mosaic , 2015, Proceedings of the National Academy of Sciences.

[50]  Stephan Hamann,et al.  Sex differences in brain activation to emotional stimuli: A meta-analysis of neuroimaging studies , 2012, Neuropsychologia.